Archive for February, 2020

Audentes Therapeutics, an Astellas company, announced it is building a gene therapy manufacturing plant in Sanford, North Carolina.

The company is investing $109 million in a new 135,000-square-feet facility, with the initial phase to take place over about 18 months. It is planned to go into operation in 2021. It is expected to create more than 200 new jobs in Lee County, North Carolina. Hiring is expected to start this year.

Our investment in large-scale manufacturing has always been a cornerstone of our strategy to develop and ultimately deliver our important genetic medicines to patients as rapidly as possible, said Natalie Holles, president and chief executive officer of Audentes. This new facility in Sanford will support the next phase of our growth as we establish a robust, global supply chain and expand our therapeutic and geographic scope as a part of the Astellas group of companies. We are excited to join the vibrant biopharmaceutical research and manufacturing community that the state of North Carolina has established.

Audentes is headquartered in San Francisco and focuses on gene therapy. It was acquired by Tokyo-based Astellas Pharma in January.

No specifics were given about what the site will manufacture. In October 2019, Audentes announced positive data from ASPIRO, the clinical trial of AT132 in patients with X-Linked Myotubular Myopathy (XLMTM). AT132 is an AAV8 vector that contains a functional copy of the MTM1 gene. XLMTM is a serious, life-threatening, rare neuromuscular disease marked by extreme muscle weakness, respiratory failure and early death.

The company indicates it hopes to submit a Biologics License Application (BLA) for AT132 to the U.S. Food and Drug Administration (FDA) later this year.

An announcement ceremony was held in the industrial shell building the company is buying in the Central Carolina Enterprise Park. It is about 45 miles southwest of Raleigh.

Gov. Roy Cooper stated, With our powerhouse research centers and highly skilled workforce, biotech pioneers recognize North Carolinas role as a leader in the life sciences. Lee County is a perfect fit for Audentes as they seek to become a global leader in genetic medicines.

The employees at the new factory are expected to earn an average salary of $83,900, which is a little over twice the Lee County average of $41,800. If Audentes hits hiring milestones, it will qualify for a state Job Development Investment Grant worth up to $3.7 million.

The county and the city of Sanford are also offering $5.7 million incentives, which includes almost $400,000 in training support from the North Carolina Community College System.

Audentes chose the location over California, Massachusetts and Colorado.

In every interaction, I was impressed with Audentes patient-centric approach to developing their AAV-based gene therapy to transform the lives of affected patients and families, said Laura Rowley, NCBiotechs director of life science economic development. She led the Centers outreach activity with Audentes. Their decision to grow in North Carolina reflects the Research Triangle regions specialized training capabilities and strengths in gene therapy and biomanufacturing. The passion and focus of the Audentes team makes me confident that they will be an outstanding addition to North Carolinas gene therapy community.

Audentes is acting as the Center of Excellence for Astellas newly founded Genetic Regulation Primary Focus.

Audentes Therapeutics is joining one of the nations top life science clusters, said Anthony M. Copeland, North Carolinas Commerce Secretary. North Carolina has the largest biomanufacturing workforce in the nation and a growing concentration of gene therapy scientists, researchers and workers.

The site of the new plant is quite close to Pfizers new gene therapy campus, which is under construction. That $600 million research and manufacturing facility has a 230-acre campus in Sanford and will employ 340 people.

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Audentes to Build $109 Million Gene Therapy Factory in North Carolina - BioSpace

Image caption Matthew Wood hopes the gene therapy will help him keep his remaining vision

A new gene therapy has been used to treat patients with a rare inherited eye disorder which causes blindness.

It's hoped the NHS treatment will halt sight loss and even improve vision.

Matthew Wood, 48, one of the first patients to receive the injection, told the BBC: "I value the remaining sight I have so if I can hold on to that it would be a big thing for me."

The treatment costs around 600,000 but NHS England has agreed a discounted price with the manufacturer Novartis.

Luxturna (voretigene neparvovec), has been approved by The National Institute for Health and Care Excellence (NICE), which estimates that just under 90 people in England will be eligible for the treatment.

The gene therapy is for patients who have retinal dystrophy as a result of inheriting a faulty copy of the RPE65 gene from both parents. The gene is important for providing the pigment that light sensitive cells need to absorb light. Initially this affects night vision but eventually, as the cells die, it can lead to complete blindness.

An injection is made into the back of the eye - this delivers working copies of the RPE65 gene. These are contained inside a harmless virus, which enables them to penetrate the retinal cells. Once inside the nucleus, the gene provides the instructions to make the RPE65 protein, which is essential for healthy vision.

Matthew Wood started losing his sight as a child, and is now registered blind. However, he does have some peripheral vision and can detect large objects and bright lights. He told the BBC: "Since I was a child I was continually told there was no treatment for this condition, so it's amazing to receive this gene therapy."

Mr Wood, from London, had his right eye treated during an hour-long operation at the John Radcliffe Hospital in Oxford.

His left eye will be injected in a few weeks. The surgery was carried out by Prof Robert MacLaren, who has pioneered research into gene therapies for preventing blindness.

He told the BBC: "This is very exciting - this is the first approved NHS gene therapy for an eye disease, but there are opportunities to use gene therapy to treat other diseases in future, not only in the eye."

The treatment is only suitable for patients who have some remaining vision. It should bring the biggest benefits to children with RPE65 retinal dystrophy, as it could halt sight loss before permanent damage is done.

It is not known how long the benefits of the treatment will last, but it's thought it could be several decades.

Jake Ternent, 23, from Durham, had his gene therapy at Moorfields Eye Hospital in London.

Like Matthew Wood, he is registered blind, but has some limited sight. He told the BBC: "I hope the treatment could improve my night vision, and possibly even my day vision, which would be incredible. I feel lucky and privileged to get this on the NHS."

Prof James Bainbridge - from Moorfields Eye Hospital - who treated Jake, told the BBC: "To be at the point now where we are able to offer this treatment on the NHS, is truly remarkable. This is the first example of what's anticipated to be a whole new generation of treatments."

It will take a month or two before Matthew and Jake know what changes the gene therapy has made to their vision. But even if it simply prevents further sight loss, both say they will be delighted.

Professor Stephen Powis, NHS medical director, said: "Loss of vision can have a devastating effect, particularly for children and young people, but this truly life-changing treatment offers hope to people with this rare and distressing condition."

Follow Fergus on Twitter.

More here:
Gene therapy to halt rare form of sight loss - BBC News

Industry leaders, patient advocates, researchers unite to maximize the incredible potential of transformative gene therapies

WASHINGTON--(BUSINESS WIRE)-- The Institute for Gene Therapies (IGT) launched today with a focus on advocating for a modernize the U.S. regulatory and reimbursement framework so that gene therapies can deliver their significant potential to patients. IGT will educate stakeholders across the healthcare community about the transformational nature of gene therapies and advocate for policies that help ensure patients who need them can benefit from them.

Gene therapy is poised to change human health as we know it. By altering non-functioning genes or replacing absent ones, gene therapies have the potential to reshape the way thousands of diseases are treated with long-lasting effects for patients. The first of these transformative therapies have already been approved by the U.S. Food and Drug Administration (FDA) and hundreds more are currently being studied in clinical trials for rare and common diseases, including many types of cancer, neuromuscular diseases, blood disorders and infectious diseases, among others.

Many crippling conditions like Charcot-Marie-Tooth, which I was diagnosed with before the age of two take hold at a very young age, cut lives far too short or cause ongoing daily suffering, said Susan Ruediger, CEO of the CMT Research Foundation (CMTRF) and member of the IGT Patient Advocacy Advisory Council. Like so many diseases, CMT currently has no cure. I am proud to stand with other leading patient advocates, members of the research community and companies that are developing gene therapies to help ensure patients can fully realize the benefits of these giant leaps toward treatments and cures.

Gene therapies are fundamentally different from traditional pharmaceutical and biologic medicines in that they target the cause of the disease at the DNA level to create a change in the body. Further, some gene therapies are designed to be one-time treatments that offer life-long benefits. Today, the vast majority of medicines help manage the symptoms of disease over time rather than address or halt diseases at their root. The U.S. healthcare system from the drug approval process to the way treatments are paid for reflects this reality. The existing regulatory and reimbursement structures, which were established and adjusted over time to accommodate pharmaceutical and biologic medicines, need revisiting in light of gene therapies and their significant potential.

The incredible scientific advancements in this space present unique opportunities to directly improve and save the lives of patients suffering from debilitating diseases, said IGT Chairman, and former Congressman Erik Paulsen. This is not some far-off future patients are already benefiting from the first FDA-approved gene therapies. But we need policy to move faster toward this new reality where we can treat the causes of many diseases. The Institute for Gene Therapies and our members believe unique regulatory and reimbursement structures need to be established, novel development pathways need to be embraced and new value-based arrangements need to be tested.

As part of IGTs effort, experts from across the healthcare system will work together to ensure health policies reflect the latest medical advances, remove barriers that hinder patient access to gene therapies and advocate for sustainable, long-term solutions. IGT will work to ensure a greater understanding about the value gene therapies bring to patients, families, the healthcare system and our society so that gene therapies can achieve their full potential.

About the Institute for Gene Therapies

The Institute for Gene Therapies (IGT) works with stakeholders across the healthcare system to advocate for a modernized regulatory and reimbursement framework that encourages the development of transformative gene therapies and promotes patient access. Members of our advisory councils include Johnson & Johnson, PTC Therapeutics, Sarepta Therapeutics, Spark Therapeutics, Patient Advocate Foundation, Cure SMA, CMT Research Foundation, American Autoimmune Related Diseases Association (AARDA), Khrystal Davis, Founder of Texas Rare Alliance, Jenn McNary, Founder of One Rare, Seth Rotberg, Co-Founder and Head of Strategy & Engagement of Our Odyssey, Rolf Benirschke, Patient Advocate for Crohns disease, ulcerative colitis, colorectal and bladder cancer, Friedreichs Ataxia Research Alliance, and Foundation Fighting Blindness. For more information, visit gene-therapies.org and follow us on Twitter @gene_therapies

View source version on businesswire.com: https://www.businesswire.com/news/home/20200219005526/en/

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New Institute Launched to Ensure the US Healthcare System Is Ready for Gene Therapies - BioSpace

Scientists have explored the effectiveness of replacing mutated genes in mice with congenital blindness.

Describing their findings in Nature Communications, researchers highlighted that replacing a mutated sequence in blind mice resulted in approximately 10% of photoreceptors being rescued.

Following the procedure, the light sensitivity and visual acuity of the mice improved.

The new approach is an alternative strategy to gene supplementation, which has limitations when treating patients with defects in larger genes.

Koji Nishiguchi, from Tohoku Universitys department of advanced ophthalmic medicine, explained that the new technique enables the replacement of a mutated sequence with its healthy counterpart.

The platform paves the way for treating patients with mutations in larger genes, which comprise the vast majority of those with inherited retinal degeneration. Furthermore, a similar approach can be applied to treat almost any ocular and non-ocular inherited conditions, he shared.

The research team are developing the genome editing platform for application in patients with retinitis pigmentosa. A clinical trial could be undertaken by 2025.

Image credit: Pixabay/Arek Socha

See the article here:
Mice display improvements in vision following gene therapy - AOP

Abstract

Vascular dysfunction is a typical characteristic of aging, but its contributing roles to systemic aging and the therapeutic potential are lacking experimental evidence. Here, we generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome (HGPS) LmnaG609G mutation, called progerin. The Lmnaf/f;TC mice with progerin expression induced by Tie2-Cre exhibit defective microvasculature and neovascularization, accelerated aging, and shortened life span. Single-cell transcriptomic analysis of murine lung endothelial cells revealed a substantial up-regulation of inflammatory response. Molecularly, progerin interacts and destabilizes deacylase Sirt7; ectopic expression of Sirt7 alleviates the inflammatory response caused by progerin in endothelial cells. Vascular endotheliumtargeted Sirt7 gene therapy, driven by an ICAM2 promoter, improves neovascularization, ameliorates aging features, and extends life span in Lmnaf/f;TC mice. These data support endothelial dysfunction as a primary trigger of systemic aging and highlight gene therapy as a potential strategy for the clinical treatment of HGPS and age-related vascular dysfunction.

Aging represents the largest risk factor for many age-related diseases, as exemplified by cardiovascular diseases (CVDs) (1). The blood vessel consists of the tunica intima [composed of endothelial cells (ECs)], the tunica media [composed of vascular smooth muscle cells (VSMCs)], and the tunica adventitia (consisting of connective tissue) (2). The endothelium separates the vessel wall from blood flow and has an irreplaceable role in regulating vascular tone and homeostasis. Age-related functional decline in ECs and VSMCs is a main cause of CVDs (3). ECs secrete various vasodilators and vasoconstrictors that act on VSMCs and induce blood vessel contraction and relaxation (4). For instance, nitric oxide (NO) is synthesized from l-arginine by endothelial NO synthase (eNOS) and then released on VSMCs to induce blood vessel relaxation (5). When ECs become senescent or dysfunctional, vasoconstrictive, procoagulative, and proinflammatory cytokines are released; this effect reduces NO bioavailability and, in turn, increases vascular intimal permeability and EC migration (6). Despite advances in the understanding of mechanisms of endothelial dysfunction, it is unclear whether it directly triggers organismal aging.

Accumulating evidences suggest that the mechanisms underlying physiological aging are similar to those governing Hutchinson-Gilford progeria syndrome (HGPS)a premature aging syndrome in which affected patients typically succumb to CVDs (7). HGPS is predominantly caused by an a.c. 1824 C>T, p. G608G mutation in LMNA gene, which activates an alternate splicing event and generates a 50amino acid truncated form of Lamin A, referred to as progerin (8). The murine LmnaG609G, which is equivalent to LMNAG608G in humans, causes aging phenotypes resembling HGPS (9). It has been shown that progerin targets SMCs and causes blood vessel calcification and atherosclerosis (10, 11). Recent work by two groups showed that SMC-specific progerin knock-in (KI) mice are healthy and have a normal life span but suffer from blood vessel calcification, atherosclerosis, and shortened life span when crossed to Apoe/ mice (12, 13). In contrast to SMCs, the contributing roles of the vascular endothelium (VE) to systemic/organismal aging are still elusive. To address these issues, we generated a conditional progerin (LmnaG609G) KI model, i.e., Lmnaf/f mice. In combination with E2A-Cre and Tie2-Cre mice, in which the expression of Cre is ubiquitous including germ cells (14) or driven by the endothelial-specific Tie2 promoter (15), we aimed to investigate the roles of VE dysfunction to systemic aging and the targeting potential for the clinical treatment of HGPS.

To study the mechanism of VE aging, we generated a mouse model of conditional progerin KI, in which the LmnaG609G mutation, equivalent to HGPS LMNAG608G, was flanked with loxP sites, i.e., Lmnaf/f mice (fig. S1A). The Lmnaf/f mice were crossed to E2A-Cre mice, in which the Cre recombinase is ubiquitously expressed including germ cells, to generate LmnaG609G/G609G and LmnaG609G/+ mice. Progerin was ubiquitously expressed in LmnaG609G/G609G and LmnaG609G/+ mice, which recapitulated many progeroid features found in HGPS, including growth retardation and shortened life span (fig. S1, B to D).

To understand primary alterations in the VE, we isolated CD31+ murine lung ECs (MLECs) (16) from three pairs of LmnaG609G/G609G (G609G) and Lmnaf/f (Flox) mice by fluorescence-activated cell sorting (FACS) (Fig. 1A) and performed 10 Genomics single-cell RNA sequencing. We recovered 6004 cells (4137 from G609G and 1867 from Flox mice) and used the k-means clustering algorithm to cluster the cells into four groups (Fig. 1B). As expected, one group exhibited high Cd31, Cd34, and Cdh5 expression and thus largely represented MLECs. The other three groups, copurified with CD31+ MLECs by FACS, showed relatively lower Cd31 expression at the mRNA level (>10-fold lower than MLECs) but high Cd45 expression (fig. S2). Further analysis revealed that these clusters most likely contained B lymphocytes (B-like) with high Cd22, Cd81, and Ly6d expression; T lymphocytes (T-like) with high Cd3d, Cd3e, and Cd28 expression; and macrophages (M-like) with high Cd14, Cd68, and Cd282 expression (Fig. 1C). Most of the marker gene expression levels were comparable between G609G and Flox mice, except for Cd34 and Icam1, which were significantly elevated in G609G ECs, and Cd14 and Vcam1, which were increased in G609G M-like cells (Fig. 1D). Of note, Icam1 and Vcam1 are among the most conserved markers of endothelial senescence and atherosclerosis (17). Thus, we established an Lmnaf/f conditional progerin KI mouse model and revealed a unique EC population for mechanistic study.

(A) Purity analysis of sorted CD31+ MLECs by FACS. SSC, side scatter; FSC, forward scatter; PE, phycoerythrin. (B) t-Distributed stochastic neighbor embedding (t-SNE) projection of CD31+ cells revealed four clusters: ECs (green), B lymphocytes (B-like; orange), T lymphocytes (T-like; blue), and macrophages (M-like; red). (C) Marker gene expression in the four clusters: ECs (Cd31, Cd34, and Cdh5), B-like (Ly6d, Cd22, and Cd81), T-like (Cd3d, Cd3e, and Cd28), and M-like (Cd14, Cd68, and Cd282). (D) Heatmap showing marker gene expression levels in LmnaG609G/G609G (G609G) and Lmnaf/f (Flox) mice.

Of the four clusters of CD31+ MLECs, ECs and M-like cells showed high levels of p21Cip1/Waf1 (fig. S2A), a typical senescence marker (18). This finding suggests that these cells are the main target of progerin in the context of aging. A previous study reported that M-specific progerin, achieved by crossing Lmnaf/+ to Lyz-Cre mice, caused minimal aging phenotypes (12), implicating that M might have only a minor role in organismal aging. We thus focused on ECs for further analysis. We recovered 899 and 445 ECs from E2A and Flox mice, respectively (Fig. 2A). Genes with >1.5-fold change in expression between these mice were chosen for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. We observed a significant enrichment in the pathways that regulate chemotaxis, immune responses in malaria and Chagas diseases, inflammatory bowel disease, and rheumatoid arthritis and pathways essential for cardiac function (Fig. 2, B to D). To confirm this observation and to exclude paracrine effects from other cell types, we overexpressed progerin in human umbilical vein ECs (HUVECs) and analyzed representative genes by quantitative polymerase chain reaction (PCR). Most of the examined genes, e.g., IL6, IL8, IL15, CXCL1, IL1, etc., were significantly up-regulated upon ectopic progerin overexpression (Fig. 2E). Together, these data suggest that progerin causes an inflammatory response in VE, which might lead to systemic aging.

(A) t-SNE projection of LmnaG609G/G609G (G609G; green) and Lmnaf/f (Flox; orange) CD31+ MLECs according to transcriptomic data. (B to D) GO and KEGG pathway enrichment of differentially expressed genes between G609G and Flox cells. LmnaG609G/G609G MLECs show enrichment in genes that regulate the inflammatory response (C) and genes related to heart dysfunction (D). FC, fold change; FDR, false discovery rate. (E) Quantitative PCR analysis of altered genes observed in (C) and (D) in HUVECs with ectopic expression of progerin or wild-type LMNA. Data represent means SEM. *P < 0.05, **P < 0.01, and ***P < 0.001 (Students t test).

To test whether the VE dysfunction has essential roles in systemic aging, we crossed Lmnaf/f mice to a Tie2-Cre line to generate Lmnaf/f;TC mice, in which the expression of Cre recombinase is driven by the promoter/enhancer of endothelial-specific Tie2 gene (15). Single-cell transcriptome analysis confirmed that Tie2 was mainly detected in ECs (fig. S2B). Consistently, progerin was observed in the VE of Lmnaf/f;TC, but not in that of Lmnaf/f control mice or other tissues (fig. S3). VE-specific progerin induced intima-media thickening in Lmnaf/f;TC mice, in a similar manner to total KI mice, i.e., LmnaG609G/G609G mice (Fig. 3, A and B). We performed functional analysis of the VE based on acetylcholine (ACh)regulated vasodilation. ACh-induced thoracic aorta relaxation was significantly compromised in Lmnaf/f;TC mice (Fig. 3C). Similar defects were observed in LmnaG609G/G609G and LmnaG609G/+ mice (Fig. 3D and fig. S4), where progerin was expressed in both ECs and SMCs (12). To gain more evidence supporting VE-specific dysfunction, we examined thoracic aorta relaxation induced by sodium nitroprusside (SNP), which is an SMC-dependent vasodilator. Little difference was observed in thoracic aorta vasodilation in LmnaG609G/G609G and LmnaG609G/+ compared to Lmnaf/f control mice (Fig. 3E and fig. S4), supporting the notion that the VE dysfunction is a key contributor of vasodilation defects in progeria mice. As NO is the most potent vasodilator (19), we examined eNOS levels in the thoracic aorta of Lmnaf/f;TC and Lmnaf/f control mice. As expected, the level of eNOS was significantly reduced in Lmnaf/f;TC mice compared to Lmnaf/f control mice (Fig. 3F). Thus, the data confer a VE-specific dysfunction in progeria mice.

(A and B) Hematoxylin and eosin staining of thoracic aorta sections from (A) Lmnaf/f;TC and (B) LmnaG609G/G609G and Lmnaf/f control mice showing intima-media thickening. Scale bar, 20 m. (C) ACh-induced thoracic aorta vasodilation in Lmnaf/f;TC and Lmnaf/f control mice. **P < 0.01. 5-HT, 5-hydroxytryptamine. (D) ACh-induced thoracic aorta vasodilation in LmnaG609G/G609G and control mice. **P < 0.01. (E) SNP-induced thoracic aorta vasodilation in LmnaG609G/G609G and control mice. (F) eNOS level in thoracic aorta sections from Lmnaf/f;TC and control mice. Scale bar, 20 m. (G) Immunofluorescence staining (left) and quantification (right) of CD31+ gastrocnemius muscle in Lmnaf/f;TC and Lmnaf/f mice. Scale bar, 50 m. DAPI, 4,6-diamidino-2-phenylindole. (H) CD31 immunofluorescence staining in Lmnaf/f;TC and Lmnaf/f liver. Scale bar, 50 m. (I) Representative microcirculation images (left) and quantification of blood flow recovery (right) following hindlimb ischemia in Lmnaf/f;TC and Lmnaf/f mice. (J) Representative transverse sections and quantification of CD31+ gastrocnemius muscle 14 days after femoral artery ligation. Scale bar, 50 m. All data represent means SEM. P values were calculated by Students t test. Photo credits: Shimin Sun, School of Life Sciences, Shandong University of Technology; Medical Research Center, Shenzhen University (A, B, F, H, and J); Weifeng Qin, Medical Research Center, Shenzhen University (G and I).

The reduced capillary density and neovascularization capacity are both characteristics of endothelial dysfunction (1). We examined the microvasculature in various tissues of Lmnaf/f;TC mice by immunofluorescence staining. We observed a significant loss in CD31+ ECs in Lmnaf/f;TC mice compared to controls (Fig. 3, G and H). We further examined ischemia-induced neovascularization ability in Lmnaf/f;TC mice following femoral artery ligation. Limb perfusion after ischemia was significantly blunted in Lmnaf/f;TC mice compared to controls (Fig. 3I). Histological analysis confirmed that the defect in blood flow recovery in Lmnaf/f;TC mice was a reflection of an impaired ability to form new blood vessels in the ischemic region (Fig. 3J). Together, Lmnaf/f;TC mice are characterized by a loss of ECs, a reduced capillary density, and defective neovascularization capacity.

The single-cell transcriptome implicates heart dysfunction in LmnaG609G/G609G mice (Fig. 2). A correlation with gene alterations associated with atherosclerosis and osteoporosis was obvious in LmnaG609G/G609G ECs (the Online Mendelian Inheritance in Man; https://omim.org) (fig. S5). We thus reasoned that endothelial-specific dysfunction might be enough to trigger systemic aging. Notably, atherosclerosis was prominent in Lmnaf/f;TC mice (aorta atheromatous plaque observed in all nine examined mice; Fig. 4A), as well as severe fibrosis in the arteries and hearts (Fig. 4, B and C); both are typical features of aging. Moreover, the heart/body weight ratio was significantly increased in Lmnaf/f;TC compared to Lmnaf/f control mice (Fig. 4D), indicating dilated cardiomyopathy (20). Echocardiography confirmed that heart rate, cardiac output, left ventricular ejection fraction, and fractional shortening were significantly reduced in 7- to 8-month-old Lmnaf/f;TC compared to Lmnaf/f control mice. The running endurance was largely compromised in Lmnaf/f;TC mice (Fig. 4E), which is likely a reflection of amyotrophy. Moreover, the microcomputed tomography (CT) identified a decrease in trabecular bone volume/tissue volume, trabecular thickness, and trabecular number but an increase in trabecular separation in Lmnaf/f;TC mice (Fig. 4F), indicative of osteoporosis, which is an important hallmark of systemic aging (21). The VE-specific dysfunction not only accelerated aging in various tissues/organs but also shortened the median life span of Lmnaf/f;TC mice (24 weeks) to a similar extent to LmnaG609G/G609G mice (21 weeks) (Fig. 4G). LmnaG609G/G609G mice suffered from body weight loss roughly from 8 weeks of age, while Lmnaf/f;TC mice only showed a slight drop in body weight (Fig. 4H), suggesting that body weight loss itself is a less likely primary causal factor to progeria compared to endothelial dysfunction. Together, these results implicate that endothelial dysfunction, at least in progeria, acts as a causal factor of systemic aging.

(A to C) Masson trichrome staining showing an atheromatous plaque in the aorta (A), SMC loss (B), and cardiac fibrosis (C) in Lmnaf/f;TC mice. Scale bar, 20 m. (D) Heart weight and echocardiographic parameters, including heart rate, cardiac output, left ventricular (LV) ejection fraction (LVEF), and left ventricular ejection shortening (LVFS). *P < 0.05, Lmnaf/f;TC versus Lmnaf/f mice. (E) Decreased running endurance in Lmnaf/f;TC mice. ***P < 0.001. (F) Micro-CT analysis showing a decrease in trabecular bone volume/tissue volume (BV/TV), trabecular number, and trabecular thickness and an increase in trabecular separation in Lmnaf/f;TC mice. *P < 0.05, Lmnaf/f;TC versus Lmnaf/f mice. (G) Life span of LmnaG609G/G609G, LmnaG609G/+, Lmnaf/f;TC, and Lmnaf/f mice. (H) Body weight of male LmnaG609G/G609G, LmnaG609G/+, Lmnaf/f;TC, and Lmnaf/f mice. *P < 0.05, Lmnaf/f;TC versus Lmnaf/f mice; ***P < 0.001, LmnaG609G/G609G versus Lmnaf/f mice. All data represent means SEM. P values were calculated by Students t test, except that statistical comparison of the survival data was performed by log-rank test. Photo credits: Weifeng Qin, Medical Research Center, Shenzhen University (A and B); Shimin Sun, School of Life Sciences, Shandong University of Technology; Medical Research Center, Shenzhen University (C).

Loss of Sirt7, an NAD+ (nicotinamide adenine dinucleotide)dependent deacylase, causes heart dysfunction with systemic inflammation and accelerates aging (22, 23). We noticed defective neovascularization in Sirt7 knockout mice (Fig. 5A). Knockdown of Sirt7 up-regulated the levels of interleukin-1 (IL-1) and IL6 in HUVECs, as determined by Western blotting and real-time PCR (Fig. 5, B and C). Significantly, the protein level of Sirt7 was reduced almost 50% in Lmnaf/f;TC MLECs (Fig. 5D). By contrast, the levels of Sirt6 and Sirt1 were hardly decreased in Lmnaf/f;TC MLECs. Furthermore, co-immunoprecipitation revealed that Lamin A interacted with Sirt7, which was significantly enhanced in the case of progerin (Fig. 5E). FLAG-SIRT7 was polyubiquitinated, which was enhanced in the presence of progerin compared with Lamin A (Fig. 5F). Ectopic expression of progerin in human embryonic kidney (HEK) 293 accelerated SIRT7 protein degradation, which was inhibited by MG132 (a proteasome inhibitor) (Fig. 5G). These data suggest that accumulation of progerin destabilizes Sirt7 by proteasomal pathway in progeria cells.

(A) Quantification of blood flow recovery following hindlimb ischemia in Sirt7/ and Sirt7+/+ mice. (B) Left: Representative immunoblots showing indicated protein levels in HUVECs treated with si-SIRT7 or scramble (Scram). Right: Quantification of relative protein levels. *P < 0.05 and **P < 0.01, small interfering RNA (siRNA) versus Scram. GAPDH, glyceraldehyde-3-phosphate dehydrogenase. (C) Real-time PCR analysis of the indicated gene expression in HUVECs treated with si-SIRT7 or Scram. *P < 0.05, siRNA versus Scram. (D) Left: Representative immunoblots showing indicated sirtuin protein levels in FACS-sorted MLECs. Right: Quantification of relative protein levels. *P < 0.05. Note that down-regulated Sirt7 but rather up-regulated Sirt6 and hardly changed SIRT1 in Lmnaf/f;TC MLECs. (E) Left: Co-immunoprecipitation (IP) experiments showing hemagglutinin (HA)SIRT7 in antiFLAGLamin A and antiFLAG-progerin immunoprecipitates. Right: Quantification of relative protein levels. *P < 0.05. (F) Left: Representative immunoblots showing polyubiquitinated SIRT7, which was up-regulated in the presence of progerin but rather down-regulated in the presence of Lamin A. Right: Quantification of relative protein levels. *P < 0.05. (G) Representative immunoblots showing SIRT7 protein levels in the presence of Lamin A or progerin in HEK293 cells treated with cycloheximide (CHX) and/or MG132 (M). Quantification of relative SIRT7 protein levels was shown. *P < 0.05, progerin versus Lamin A. All data represent means SEM. P values were calculated by Students t test. Photo credit: Xiaolong Tang, Medical Research Center, Shenzhen University (B, D, E, F, and G).

We reasoned that Sirt7 might underlie the VE dysfunction in progeria mice. To test this hypothesis, we first examined whether ectopic Sirt7 could rescue the exacerbated inflammatory response in HUVECs. As shown, overexpression of SIRT7 significantly down-regulated the expression of multiple inflammatory genes such as IL1 (Fig. 6A). To test the in vivo function of Sirt7 in defective neovascularization, we generated a recombinant AAV serotype 1 (rAAV1) cassette with Sirt7 gene expression driven by a synthetic ICAM2 promoter (IS7O), which ensures VE-specific expression (24, 25). As shown, on-site injection of IS7O at a dose of 1.25 1010 viral genome-containing particles (vg)/50 l significantly improved blood vessel formation in Lmnaf/f;TC mice (Fig. 6B). The ectopic expression of Sirt7 and the increase in CD31-labeled ECs were evidenced by fluorescence confocal microscopy in ECs of regenerated blood vessels (Fig. 6, C and D).

(A) Real-time PCR analysis of genes that are aberrantly up-regulated in progerin-overexpressing HUVECs upon overexpression of SIRT7. *P < 0.05, **P < 0.01, and ***P < 0.001. (B) Neovascularization assay in Lmnaf/f;TC mice with hindlimb ischemia, treated with or without IS7O particles. **P < 0.01. (C) Immunofluorescence microscopy analysis of FLAG-SIRT7 and CD31 expression in gastrocnemius muscle 14 days after femoral artery ligation. Scale bar, 25 m. (D) Percent CD31+ ECs in Lmnaf/f;TC mice treated with or without IS7O particles. ***P < 0.001. (E) Representative immunofluorescence images of the liver, aorta, and muscle of Lmnaf/f;TC mice after IS7O therapy, showing CD31+ ECs with FLAG-SIRT7 expression. Scale bar, 50 m. (F) Representative immunoblots showing expression of FLAG-SIRT7 in aorta and WBMCs. Note that FLAG-SIRT7 was merely detected in WBMCs. (G) Life span of IS7O-treated and untreated Lmnaf/f;TC and LmnaG609G/+ mice. (H) Body weight of IS7O-treated and untreated Lmnaf/f;TC and Lmnaf/f mice. All data represent means SEM. P values were calculated by Students t test, except that the statistical comparison of survival data was performed by log-rank test. Photo credits: Shimin Sun, School of Life Sciences, Shandong University of Technology; Medical Research Center, Shenzhen University (C and E); Xiaolong Tang, Medical Research Center, Shenzhen University (F).

We next asked whether IS7O could ameliorate premature aging and extend life span. To this end, the IS7O particles were injected via tail vein from 21 weeks of age, when progeria mice start to die. The injection was repeated every other week at a concentration of 5 1010 vg/200 l per mouse. While all untreated mice died before 34 weeks of age, most IS7O-treated mice were still alive at the age of 44 weeks, when they were euthanized for histological analysis. The ectopic expression of FLAG-SIRT7 was observed in the ECs of liver, muscle, and aorta, but not in whole bone marrow cells (WBMCs), determined by fluorescence microscopy and/or Western blotting (Fig. 6, E and F). The median life span was extended by 76%from 25 to >44 weeks (Fig. 6G). The age-related body weight loss was slightly rescued upon IS7O therapy in Lmnaf/f;TC mice (Fig. 6H). These data suggest that progerin-caused VE dysfunction and systemic aging are partially, if not entirely, attributable to Sirt7 decline.

Mounting evidence supports the idea that endothelial dysfunction is a conspicuous marker for vascular aging and CVDs (2628). However, the fundamental question whether VE dysfunction causally triggers systemic aging remains. The heterogeneity of vascular cells and their close communication with the bloodstream render it difficult to understand the primary function of the VE. The murine LmnaG609G mutation, equivalent to the LMNAG608G found in humans with HGPS, causes premature aging phenotypes in various tissues and organs, thus providing an ideal model for studying aging mechanisms at both tissue and organismal levels. Data from the LmnaG609G model suggest that SMCs are the primary cause of vascular diseases, such as atherosclerosis (10, 11). A recent study showed that specific expression of LmnaG609G in SMCs causes atherosclerosis and shortens life span in atherosclerosis-prone Apoe/ mice (12). We used Tie2-Cre line to generate the VE-specific LmnaG609G mouse model. Lmnaf/f;TC mice exhibited vascular dysfunction, accelerated aging, and a shortened life span to a similar extent to the whole-body LmnaG609G model. Tie2 expression was reported not only in ECs but also in hematopoietic lineages (29). Our single-cell transcriptomic data identified Tie2 transcripts mainly in MLECs instead of B-, T-, or M-like cells. When a synthetic ICAM2 promoter was used to drive ectopic expression of FLAG-SIRT7 in the rescue experiments, ectopic FLAG-SIRT7 was successfully detected in ECs of the aorta, muscle, and liver but hardly detected in WBMCs. Therefore, Tie2-driven progerin expression combined with synthetic ICAM2-drivern SIRT7 rescue largely ensures the EC-specific contribution in systemic aging. Of note, although the number and function of hematopoietic stem cells decline in another progeria model, Zmpste24/ mice (30), little effect was observed when healthy hematopoietic progenitor cells were transplanted to Zmpste24/ mice in the context of systemic aging. Recently, Hamczyk et al. (12) found that knocking in the LmnaG609G allele in macrophages mediated by LysM-Cre merely affects aging and life span. Therefore, our data strongly suggest that, as the largest secretory organ (3), VE is pivotal in regulating systemic aging and longevity. In support of our findings, Foisner et al. (31) reported that VE-cadherin promoter-driven expression of progerin in a transgenic line causes cardiovascular abnormalities and shortens life span.

One limitation in the understanding of mechanisms of VE dysfunction is the vascular cell heterogeneity and the lack of appropriate in vitro system for ECs. Here, we took advantage of single-cell RNA sequencing technique to analyze the transcriptomes of MLECs. Unexpectedly, although >95% purity was achieved by FACS, MLECs isolated by CD31 immunofluorescence labeling turned out to be a mixture of cells, including ECs and T-, B-, and M-like cells. Although enriched by FACS, these non-ECs expressed low level of CD31 mRNA, raising the possibility that cell surface proteins such as CD31 T-, B-, and M-like cells might be obtained from neighbor ECs via intercellular protein transfer (32). Nevertheless, these findings suggest that one cannot just purify CD31+ cells and pool them together for mechanistic study, because one might arrive at a misleading conclusion. We compared the expression of genes that are associated with atherosclerosis, arthritis, heart failure, osteoporosis, or amyotrophy (the Online Mendelian Inheritance in Man; https://omim.org) between progeroid and control in all four clusters. An obvious alteration of these genes/pathways was observed mainly in ECs and M-like cells (fig. S2). At the current stage, it is hard to separate cell-autonomous and paracrine effects among different cell populations. In the future, it would be worthwhile to do an analysis in Lmnaf/f;TC MLECs. The data will be useful to study the paracrine effect of ECs on other cell populations.

Since the identification of the causal link between LMNA G608G mutation and HGPS, numerous efforts have been put on the development of treatment for HGPS. Farnesyltransferase inhibitors (33), resveratrol, and N-acetyl cysteine (30) treatment alleviate premature aging features and extend life span in progeria murine models. Rapamycin (34) and metformin (35) incubation rescue senescence in HGPS cells. On the basis of these notions, patients with HGPS taking a farnesyltransferase inhibitor, lonafarnib, in a clinical trial showed significant improvement of health status, reduction of mortality rate, and a potential extension of life span (about 1 to 2 years) (36). Taking advantage of gene therapy and the dispensable role of Lamin A, morpholino oligos (9), and CRISPR-Cas9 designs (37, 38), which prevent Lamin A/progerin generation, can alleviate aging features and extend life span from 25 to 40% in progeria mice. However, considering the indispensable function of Lamin A in humans, these genome-modifying strategies need further experimentation before potential clinical application. Here, applying a different strategy, we showed that rAAV1-SIRT7 (IS7O), targeting dysfunctional VE, largely ameliorates progeroid features and almost doubles the median life span (from 25 to >44 weeks). To our best knowledge, this is the most marked rescue of progeria in a mouse model via gene therapy. Given that SIRT7 elicits deacylase activity to modulate cellular functions (22, 23), it is worthwhile to identify small molecules that specifically target SIRT7 activity for therapeutics in the future. Resveratrol is a potential activator of SIRT1, as well as SIRT7 (39), and has protective effects on vascular function and blood pressure (40). Further depicting the relationship of SIRT7 and resveratrol in the regulation of vascular function would help in seeking leading compounds of SIRT7 specific activators.

Collectively, we reveal VE dysfunction as a primary trigger of systemic aging and as a risk factor for age-related diseases such as atherosclerosis, heart failure, and osteoporosis. Drugs and molecules that target VE might serve as good candidates in the treatment of age-related diseases other than CVDs. The findings in SIRT7-based gene therapy implicate great clinical potentials for progeria as well as in antiaging applications.

Lmnaf/+ allele (LmnaG609G mutation flanked by two loxP sites) was generated by Cyagen Biosciences Inc., China. Briefly, the 5 and 3 homology arms were amplified from bacterial artificial chromosome clones RP23-21K15 and RP23-174J9, respectively. The G609G (GGC to GGT) mutation was introduced into exon 11 in the 3 homology arm. C57BL/6 embryonic stem cells were used for gene targeting. To obtain ubiquitous expression of progerin (LmnaG609G/G609G), Lmnaf/f mice were bred with E2A-Cre mice. To obtain VE-specific expression of progerin, Lmnaf/f mice were bred with Tie2-cre mice. Mice were housed and handled in accordance with protocols approved by the Committee on the Use of Live Animals in Teaching and Research of Shenzhen University, China.

Four-month-old male mice were anesthetized with 4% chloral hydrate (0.20 ml/20 g) by intraperitoneal injection. Hindlimb ischemia was performed by unilateral femoral artery ligation and excision, as previously described (41). In brief, the neurovascular pedicle was visualized under a light microscope following a 1-cm incision in the skin of the left hindlimb. Ligations were made in the left femoral artery proximal to the superficial epigastric artery branch and anterior to the saphenous artery. Then, the femoral artery and the attached branches between ligations were excised. The skin was closed using a 4-0 suture line, and erythromycin ointment was applied to prevent wound infection after surgery. Recovery of the blood flow was evaluated before and after surgery using a dynamic microcirculation imaging system (Teksqray, Shenzhen, China). Relative blood flow recovery is expressed as the ischemia-to-nonischemia ratio. At least three mice were included in each experimental group.

HEK293 cells and HUVECs were purchased from the American Type Culture Collection. HEK293 cells were cultured in Gibco Dulbeccos modified Eagles medium (Life Technologies, USA) supplemented with 10% fetal bovine serum at 37C, 5% CO2. HUVECs were cultured in Gibco M199 (Life Technologies, USA) supplemented with 15% fetal bovine serum, EC growth supplement (50 g/ml), and heparin (100 g/ml) at 37C, 5% CO2. All cell lines used were authenticated by short tandem repeat profile analysis and were mycoplasma free.

Total RNA was extracted from cells or mouse tissues using TRIzol reagent RNAiso Plus (Takara, Japan) and transcribed into complementary DNA (cDNA) using 5 PrimeScript RT Master Mix (Takara, Japan), following the manufacturers instructions. The mRNA levels were determined by quantitative PCR with SYBR Premix Ex Taq II (Takara, Japan) detected on a CFX Connect Real-Time PCR Detection System (Bio-Rad). All primer sequences are listed in table S1.

For protein extraction, cells were suspended in SDS lysis buffer and boiled. Then, the lysate was centrifuged at 12,000g for 2 min, and the supernatant was collected. For Western blotting, protein samples were separated on SDS-polyacrylamide gels, transferred to polyvinylidene difluoride membranes (Millipore, USA), blocked with 5% nonfat milk, and incubated with the relevant antibodies. Images were acquired on a Bio-Rad system. All antibodies are listed in table S2.

Frozen sections of aorta, skeletal muscle, and liver tissues were fixed in 4% paraformaldehyde (PFA), permeabilized with 0.3% Triton X-100, blocked with 5% bovine serum albumin and 1% goat serum, and then incubated with primary antibodies at room temperature for 2 hours or at 4C overnight. After three washes with phosphate-buffered saline with Tween 20, the sections were incubated with secondary antibodies for 1 hour at room temperature and then stained with 4,6-diamidino-2-phenylindole antifade mounting medium. Images were captured under a Zeiss LSM 880 confocal microscope. All antibodies are listed in table S2.

Paraffin-embedded sections of PFA-fixed tissues were dewaxed and hydrated. Staining was then performed using a Masson trichrome staining kit (Beyotime, China). In brief, the sections were dipped in Bouin buffer for 2 hours at 37C and then successively stained with Celestine blue staining solution, hematoxylin staining solution, Ponceau S staining solution, and aniline blue solution for 3 min. After dehydrating with ethyl alcohol three times, the sections were mounted with Neutral Balsam Mounting Medium (BBI Life Science, China). Images were captured under a Zeiss LSM 880 confocal microscope.

Mice were euthanized by decapitation. The lungs were then collected, cut into small pieces, and then digested with collagenase I (200 U/ml) and neutral protease (0.565 mg/ml) for 1 hour at 37C. The isolated cells were incubated with phycoerythrin-conjugated anti-CD31 antibody for 1 hour at 4C and then 7-aminoactinomycin D (7-AAD) (1:100) for 5 min. CD31-positive and 7-AADnegative cells were sorted on a flow cytometer (BD Biosciences, USA).

Four-month-old male mice were anesthetized with 4% chloral hydrate by intraperitoneal injection. Thoracic aortas were collected, rinsed in ice-cold Krebs solution, and cut into 2-mm-length rings. Each aorta ring was bathed in 5-ml oxygenated (95% O2 and 5% CO2) Krebs solution at 37C for 30 min in a myograph chamber (620M, Danish Myo Technology). Each ring was stretched in a stepwise fashion to the optimal resting tension (thoracic aortas to ~9 mN) and equilibrated for 30 min. Then, 100 mM K+ Krebs solution was added to the chambers to elicit a reference contraction and then washed out with Krebs solution at 37C until a baseline was achieved. Vasodilation induced by Ach or SNP (1 nM to 100 M) was recorded in 5-hydroxytryptamine (2 M) contracted rings. Data are represented as a percentage of force reduction and the peak of K+-induced contraction. At least three mice were included in each experimental group.

Seven- to 8-month-old male mice were anesthetized by isoflurane gas inhalation and then subjected to transthoracic echocardiography (iU22, Philips). Parameters, including heart rate, cardiac output, left ventricular posterior wall dimension, left ventricular end-diastolic dimension, left ventricular end-systolic diameter, LV ejection fraction, and LV fractional shortening, were acquired. At least three mice were included in each experimental group.

Seven- to 8-month-old male mice were euthanized by decapitation. The thigh bone was fixed in 4% PFA at 4C overnight. The relevant data were collected by micro-CT (Scanco Medical, CT100). At least three mice were included in each experimental group.

A Rota-Rod Treadmill (YLS-4C, Jinan Yiyan Scientific Research Company, China) was used to monitor fatigue resistance. Briefly, mice were placed on the rotating lane, and the speed of the rotations gradually increased to 40 rpm. When the mice were exhausted, they were safely dropped from the rotating lane, and the latency to fall was recorded. At least three mice were included in each experimental group.

CD31+ cells isolated from murine lung by FACS (>90% viability) were used for single-cell RNA sequencing. A sequence library was built according to the Chromium Single-Cell Instrument library protocol (42). Briefly, single-cell RNAs were barcoded and reverse-transcribed using the Chromium Single-Cell 3 Reagent Kits v2 (10 Genomics) and then fragmented and amplified to generate cDNAs. The cDNAs were quantified using an Agilent Bioanalyzer 2100 DNA Chip, and the library was sequenced using an Illumina Hiseq PE150 with ~10 to 30M raw data assigned for each cell. The reads were mapped to the mouse mm9 genome and analyzed using STAR: >90% reads mapped confidently to genomic regions and >50% mapped to exonic regions. Cell Ranger 2.1.0 was used to align reads, generate feature-barcode matrices, and perform clustering and gene expression analysis. Mean reads (>80,000) and 900 median genes per cell were obtained. The unique molecular identifier counts were used to quantify the gene expression levels, and the t-distributed stochastic neighbor embedding (t-SNE) algorithm was used for dimensionality reduction. The cell population was then clustered by k-means clustering (k = 4). The Log2FoldChange was the ratio of gene expression of one cluster to that of all other cells. The P value was calculated using the negative binomial test, and the false discovery rate was determined by the Benjamini-Hochberg procedure. GO and KEGG enrichment analyses were performed in DAVID version 6.8 (43).

A two-tailed Students t test was used to determine statistical significance, except that the statistical comparison of survival data was performed by log-rank test. All data are presented as the means SD or means SEM, as indicated, and a P value <0.05 was considered statistically significant.

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/6/8/eaay5556/DC1

Fig. S1. Generation of Lmnaf/f mice and phenotypic analysis of LmnaG609G/G609G mice.

Fig. S2. Single-cell transcriptomic analysis of CD31+ MLECs.

Fig. S3. VE-specific progerin expression.

Fig. S4. Vasodilation analysis of LmnaG609G/+ mice.

Fig. S5. Expression of atherosclerosis- and osteoporosis-associated genes in MLEC transcriptomes.

Table S1. List of primer sequences.

Table S2. List of antibodies.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: We thank J. Tamanini (Shenzhen University and ETediting) for editing the manuscript before submission. Funding: This study was supported by grants from the National Natural Science Foundation of China (91849208, 81571374, 91439133, 81871114, 81601215, 81972602, and 81702909), the National Key R&D Program of China (2017YFA0503900), the Science and Technology Program of Guangdong Province (2014A030308011, 2017B030301016, and 2019B030301009), and the Shenzhen Municipal Commission of Science and Technology Innovation (JCYJ20160226191451487, KQJSCX20180328093403969, JCYJ20180507182044945, ZDSYS20190902093401689, and Discipline Construction Funding of Shenzhen 2016-1452). Author contributions: B.L. designed and supervised the project. S.S., W.Q., and X.T. conducted experiments with help from W.H., S.Z., M.Q., Z.L., X.C., Q.P., and B.Z. Y.M. performed bioinformatic analysis. Z.W. and Z.Z. provided resources. S.S., X.T., and B.L. wrote the manuscript. All authors discussed the experimental results and reviewed the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. The data of single-cell transcriptomics are available in the GEO database (GSE138975). Additional data related to this paper may be requested from the authors.

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Vascular endotheliumtargeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model - Science...

Its point-of-care platform advances the development of gene-based medicine through collaborations and in-licensing

Inc () announced a collaboration with Johns Hopkins University to utilize its point-of-care platform to develop and supply gene therapies and technologies.

The companys POCare cell therapy platform is designed to advance the development of Advanced Therapy Medicinal Products medicines based on genes, tissues or cells through collaborations and in-licensing with other companies.

CEO Vered Caplan is confident in the pedigree and resources of the Baltimore research university.

JHU has unparalleled capabilities in the cell and gene therapy sector, Caplan said in a statement. Our POCare platform is designed to provide unique cell and gene therapy solutions in a cost effective, high quality and scalable manner, using closed systems and other advanced cell processing technologies at the point of care.

We look forward to utilizing our POCare platform to support JHUs growing development and processing needs in order to advance and accelerate cell and gene based clinical therapeutic research. We believe this collaboration with JHU, a clear leader in the field of cell and gene therapy, further validates the significant value proposition of our POCare platform.

Johns Hopkins is the third major institution to sign an agreement with , Caplan said. Last month, the company reached a deal with the University of California, Davis.

With its introduction of Orgenesiss POCare platform, hospitals are able to implement the company's proprietary automated, closed systems and know-how to collect, process and supply cells for various treatments such as the manufacturing of CAR-T cell therapies.

The Germantown, Maryland-based company provides centralized contract development and manufacturing organization (CDMO) services, as well as localized point-of-care development and processing centers through its subsidiary Orgenesis Maryland Inc.

Contact Andrew Kessel at [emailprotected]

Follow him on Twitter @andrew_kessel

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Orgenesis teams up with Johns Hopkins University to develop gene therapies with its POCare platform - Proactive Investors USA & Canada

Audentes Therapeutics, an Astellas company based in San Francisco, California, will open a new facility in Lee County, Governor Roy Cooper announced Tuesday.

The life-sciences company has purchased a recently-completed shell building located in Central Carolina Enterprise Park and will create 209 jobs at an average salary of $83,900. The company will be investing $109.4M in Sanford over a five year period.

With our powerhouse research centers and highly-skilled workforce, biotech pioneers recognize North Carolinas role as a leader in the life sciences, said Governor Cooper. Lee County is a perfect fit for Audentes as they seek to become a global leader in genetic medicines.

Audentes Therapeutics, Inc., an Astellas company, is an AAV-based genetic medicines company focused on developing and commercializing innovative therapies that can offer transformative benefits to patients.

In addition to its gene therapy portfolio targeting serious rare neuromuscular diseases, the company states, Audentes is leveraging Astellas global resources, industry leadership in immune biology, and deep scientific expertise to expand its reach and deliver valuable new genetic medicines to patients around the world.

Lee County Board of Commissioners Chair Amy Dalrymple gave remarks during the announcement, saying, Thank you to Audentes for recognizing the strengths of the Lee County community and for investing in us to create over 200 jobs for Central North Carolina. Lee County looks forward to working together and building a long-term partnership where Audentes and the Lee County community flourishes.

Sanford Mayor Chet Mann stated, We are overjoyed at having Audentes Therapeutics in our community. Their decision to locate here is proof that our Public / Private Partnership and the efforts toward making Sanford a desirable place to live and work have been a success. A company of this quality and the important work they do will have tremendous impact; creating a new Life Sciences cluster that will pay future dividends. We truly look forward to a great partnership with Audentes and we enthusiastically welcome them here.

Sanford Area Growth Alliance Board of Directors Chair Kirk Bradley commented, Its been a little less than 5 years since Mark Sweeney, of the site selection firm, McCallum Sweeney, addressed a group of community and Civic leaders on July 30, 2015 about how Prepared Communities Win.

This message resonated and the announcement of Audentes Therapeutics is the culmination of what can happen to a community that listens to experts and harnesses private and public capital for a common objective of economic growth.

Today Sanford, Broadway and Lee County has one of the most, if not THE most, thriving economic development eco-system in the State of North Carolina. We are honored that Governor Cooper would make this historic announcement. We welcome Audentes Therapeutics to our community as a new corporate citizen with open arms for a successful future!

Contributed

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Leading gene therapy company to invest $109M in Sanford - Sandhill Sentinel

Dive Brief:

Bluebird's commercial operations are just getting off the ground. In its latest earnings report, the Cambridge, Massachusetts-based biotech detailed how it has inked agreements with health insurers in Germany that should provide coverage for LentiGlobin, which is sold under the brand name Zyntegloin Europe, for up to 50% of eligible beta-thalassemia patients. Bluebird expects the first commercial patient to be treated before July.

Across the Atlantic, U.S. patients are looking at a longer timeline before LentiGlobin becomes available. Stifel analysts wrote in a note to clients that they don't foresee any stateside patients receiving the therapy commercially in 2020 "given what we anticipate will be a complicated negotiation process with payors."

Analysts at Raymond James, meanwhile, downgraded Bluebird to a "Market Perform" rating, writing that "execution issues on the regulatory, clinical and manufacturing side outweigh our support for the innovative drug products."

As Bluebird works through the latest delay in beta-thalassemia,it will also be preparing for an expanded research program in sickle cell. The company already intended to kick off a late-stage study in sickle cell patients with a history of vaso-occlusive crises in the first half of 2020. With Tuesday's earnings presentation, though, came plans to initiate a second late-stage study sometime this year, which will evaluate LentiGlobin's effects in about 18 children with sickle cell and elevated stroke risk.

A sickle cell approval, though a ways off, could boost Bluebird's bottom line. Beta-thalassemiais rarer in U.S. than other parts of the world, and certainly less common than sickle cell. According to estimates cited by the National Organization of Rare Disorders, roughly 3,300 U.S. patients have beta-thalassemiaversus the 100,000 who have sickle cell.

An expanded program could provide more evidence of LentiGlobin's benefit in this larger patient pool.Yet the updates don't seem to have alleviated investor concerns. Bluebird shares were down nearly 10% in late Wednesday morning, trading around $80 apiece.

"LentiGlobin in Sickle Cell Disease remains a bright spot, in our view, but with [late-stage studies] expected to get underway this year, we don't expect investor sentiment to change anytime soon," Stifel analysts wrote.

The investment bank models Zyntelgo bringing in $12 million worth of revenue in 2020 from the beta-thalassemia indication, increasing to $53 million in 2021 and $390 million by 2030. Conversely, it models $48 million in 2022 from the sickle cell indication, increasing to almost $2 billion by 2030.

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Bluebird's gene therapy hits another delay, this time in the US - BioPharma Dive

The vaccine and cell and gene therapy biomanufacturing sectors are growing at an accelerated rate with the US and Europe driving a significant segment of this growth. European biopharma and CDMO scientists often ask if we have representation in the region as they search for innovative tools to alleviate their production and QC bottlenecks; we can now finally say yes to this important question," says Dr. Sean Hart, LumaCytes Chief Executive Officer. In support of these efforts, LumaCyte has hired analytical instrumentation veteran, Christof Hasse, PhD to manage sales and service as part of its European expansion. At LumaCyte, were obsessed with delivering exceptional customer service, so having Laser Force Cytology (LFC) experts who understand our customers unique needs, and are located in the same region, is critical to delivering the highest level of service, says Rene Hart, LumaCyte President and Chief Business Officer. We are excited to have Christof on board as he brings LumaCytes transformative Laser Force Cytology to the hands of European researchers and production scientists.

About LumaCyte

LumaCyte is an advanced research and bioanalytics instrumentation company headquartered in Charlottesville, VA. LumaCyte produces label-free, single cell analysis and sorting instrumentation where the use of antibody or genetic labeling is not required for cellular analysis. This revolutionary technology utilizes Laser Force Cytology (LFC) to measure optical and fluidic forces within a microfluidic channel to identify and measure the intrinsic cellular properties of each cell. The multivariate nature of the data has enabled a host of Big Data strategies and cloud computing capabilities that drive advanced analytics, allowing a deeper understanding of cell based biological systems. Applications of LumaCyte's label-free platform technology include viral infectivity for vaccine development and manufacturing, cell and gene therapy, cancer biology R&D, CAR T cell immunotherapy, adventitious agent testing (AAT), iPSCs, infectious disease, and pre-clinical drug discovery, in addition to multiple applications across the biomanufacturing sector for quality control and process optimization.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200220005263/en/

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LumaCyte Expands into Europe Tackling Expansive Vaccine and Cell and Gene Therapy Markets - BioSpace

With more and more cell therapies entering the market, Dr Maitry Ganatra, global market development director at Thermo Fisher Scientific guides readers on how to comply with regulatory standards to ensure quality and safety, and ultimately make it to commercialisation.

In recent years, sophisticated cell therapies have emerged to treat a broad range of cardiovascular, neurological and autoimmune diseases, among others. The complexity and variability of these therapies present unique challenges for the transition from the research phase to commercialisation. Thorough consideration of current good manufacturing practice (cGMP) requirements and regulatory compliance early in the process, even during the research stage, can help alleviate the challenges involved in scaling up. Additionally, applying quality by design (QbD) principles to the production process can ensure high quality and safety of new therapeutics, making commercialisation easier.

Commercialisation of cell and gene therapies, whether allogeneic or autologous, can be challenging. In allogeneic cell therapy, where a single cell type is mass produced for treating multiple patients, the challenge is that of scaling up a thousand-fold from the research phase, while still maintaining the necessary physiological conditions. When processes get scaled up, laboratory instruments, such as centrifuges and CO2 incubators used during the research phase, may not be compatible with the requirements of the cGMP environment. Typically, when equipment designed for research purposes are used in a cGMP compliant facility without consideration of validation and documentation requirements, this can pose a huge issue during commercialisation.

Scaling up could introduce inconsistencies across multiple factors, including incubator temperature, composition of reagents, such as media or growth factors, as well as cell culture parameters, such as incubation time. Even the slightest change in production conditions upon moving from research level to the multi-liter scale can have an impact on how the cells behave, ultimately affecting the quality and safety of the therapy. In adapting research workflows to meet commercial cGMP requirements, cell therapy manufacturers often realise too late that processes that work well at the research stage are incompatible with the cGMP environment. Furthermore, they often underestimate how involved the regulatory compliance process can be; each piece of equipment needs to be validated to ensure it meets the highest standards and relevant documentation should be produced.

In autologous cell therapy, where each batch of cells is produced for only one patient, modified and re-introduced into the same patient, the challenge is that of scaling out and producing multiple batches corresponding to multiple patients, while maintaining due diligence throughout the process-heavy workflow.

Scaling out in autologous cell therapy demands more space and a large number of instruments, each being compliant with regulatory standards. The challenges here involve managing the complexity of working with multiple sets of equipment, having sufficient space for all these systems and keeping track of which instrument is used for a specific therapy. When processing multiple batches in autologous cell therapy, every patient sample needs to be tracked as it goes from the hospital to the manufacturing site and back to the patient, thereby adding logistical burden to the process. On the whole, scaling out relies on having the operational capacity to accommodate all the equipment as well as the materials, manpower and time involved in the process.

Recognising these challenges, many technology vendors offer advice and guidance around cGMP compatible instrumentation, including centrifuges, biological safety cabinets, cold storage equipment and CO2 incubators. A standard laboratory CO2 incubator, for example, cannot be moved to a cGMP environment without temperature mapping or testing for installation, operational and performance qualifications (IQ, OQ and PQ). To this effect, some vendors even offer customisable solutions to help meet cGMP requirements.

Applying quality by design principles to cell therapy manufacturing

Increased testing does not necessarily improve the quality of the final product. A more robust solution is to build quality into entire production workflows. The US Food and Drug Administration (FDA) encourages implementation of the Quality by Design (QbD) principles into the production, manufacturing and regulation processes.

In adopting the QbD principles, every step of the process, starting from raw materials to the operating plant, clean room, and water and materials used, all should adhere to high-quality standards. Every piece of equipment used in the manufacturing process needs to meet quality requirements, such as being certified by the International Organisation for Standardisation.

Recognising the challenges posed when transitioning from research to commercialisation of cell and gene therapies, many instrument vendors apply the QbD principles and undertake all of the necessary performance testing to deliver equipment that meet the requirements of cGMP compliant facilities. Some of the steps involved in performance testing include temperature testing, ramp up/ramp down testing, sterilisation, and electrical checks. By inspecting the overall safety and configuration of the instrumentation, the required factory end-of-line testing is completed.

Vendors also provide the relevant documentation required in adhering with the cGMP standards, for example, issuing the certificate of conformance and providing instrument calibration documentation, equipment drawing and critical component specifications. To ensure that each piece of equipment is installed per vendor specifications, meets the quality requirements, and offers consistent and reproducible results, IQ, OQ and PQ validation protocols are performed, followed by issuing the respective documentation.

In addition to testing for compliance and offering documentation, some vendors provide user and maintenance training to ensure best practices are upheld in the day-to-day workflow.

As pharmaceutical manufacturers transition cell therapies from the research to the commercialisation phase, they start acknowledging the complexity that comes from scaling up and expanding workflows, while staying compliant with the regulatory requirements. Carefully planning cell therapy production processes beforehand, understanding the needs of cGMP compliance and collaborating with knowledgeable technology vendors who offer solutions adhering to QbD principles, can set cell therapy manufacturers up for successful commercialisation.

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Getting cell therapies to market - EPM Magazine

- First conditional approval of ZYNTEGLOTM (autologous CD34+ cells encoding A-T87Q-globin gene) gene therapy for patients 12 years and older with transfusion-dependent -thalassemia who do not have 0/0 genotype in Europe achieved in 2019; Germany launch underway

- Announced positive top-line data from pivotal Phase 2 KarMMa study of ide-cel in relapsed and refractory multiple myeloma

- Presented clinical data across studies of LentiGlobin gene therapy for -thalassemia (betibeglogene autotemcel) and LentiGlobin gene therapy for sickle cell disease (SCD) and bb21217 in multiple myeloma at American Society of Hematology (ASH) Annual Meeting

- Ended quarter with $1.24 billion in cash, cash equivalents and marketable securities

bluebird bio, Inc. (NASDAQ: BLUE) today reported financial results and business highlights for the fourth quarter and full year ended December 31, 2019.

"2019 was truly a transformative year for bluebird, with our first commercial product now launched in Europe and exciting progress across our first four clinical programs and pipeline," said Nick Leschly, chief bluebird. "Notably, our data in SCD continues to build, and at the ASH annual meeting in December we presented data that showed a 99% reduction in the annualized rate of vaso-occlusive crises (VOC) and acute chest syndrome (ACS) in HGB-206 Group C patients with history of VOCs and ACS who had at least six months follow-up. In -thalassemia, the consistency with which patients who do not have a 0/0 genotype in our Northstar-2 (HGB-207) study are achieving transfusion independence is very encouraging and were starting to see indications that we may be able to see similar outcomes with many patients with 0/0 genotypes as well in our Northstar-3 (HGB-212 study). These data put us in a strong position as we progress our European launch, currently underway in Germany. At the end of 2019, we also announced positive top-line data from the pivotal KarMMa study of ide-cel. We and our partners at BMS look forward to submitting these data to the FDA in the first half of this year. Amidst all of our progress in 2019, our birds demonstrated time and again their dedication to patients and ability to meet and learn from the many challenges we have faced along the way. I look forward to facing the challenges of 2020 with this amazing flock."

Recent Highlights:

TRANSFUSION-DEPENDENT -THALASSEMIA

SICKLE CELL DISEASE (SCD)

MULTIPLE MYELOMA

COMPANY

Upcoming Anticipated Milestones:

Fourth Quarter and Full Year 2019 Financial Results

LentiGlobin for -thalassemia Safety

Non-serious adverse events (AEs) observed during the HGB-204, HGB-207 and HGB-212 clinical studies that were attributed to LentiGlobin for -thalassemia were hot flush, dyspnoea, abdominal pain, pain in extremities, thrombocytopenia, leukopenia, neutropenia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to LentiGlobin for -thalassemia for TDT.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

With more than five years of follow-up to date, there have been no new unexpected safety events, no deaths, no graft failure and no cases of vector-mediated replication competent lentivirus or clonal dominance. In addition, there have been no new reports of veno-occlusive liver disease (VOD) as of the data cutoff presented at ASH.

About LentiGlobin for -Thalassemia (betibeglogene autotemcel)

The European Commission granted conditional marketing authorization for LentiGlobin for -thalassemia, to be marketed as ZYNTEGLO (autologous CD34+ cells encoding A-T87Q-globin gene) gene therapy, for patients 12 years and older with TDT who do not have a 0/0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

TDT is a severe genetic disease caused by mutations in the -globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Story continues

LentiGlobin for -thalassemia adds functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

The conditional marketing authorization for ZYNTEGLO is only valid in the 28 member states of the EU as well as Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. Food and Drug Administration granted LentiGlobin for -thalassemia Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT.

bluebird bio has initiated its rolling BLA submission of LentiGlobin for -thalassemia for approval in the U.S. and is engaged with the FDA in discussions regarding the requirements and timing of certain information to be provided in the BLA, including information regarding various release assays for LentiGlobin for -thalassemia. Subject to these ongoing discussions, the company is currently planning to complete the BLA submission in the second half of 2020.

LentiGlobin for -thalassemia continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit http://www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207), NCT03207009 for Northstar-3 (HGB-212).

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for -thalassemia. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

ZYNTEGLO, LentiGlobin, and bluebird bio are trademarks of bluebird bio, Inc.

The full common name for ZYNTEGLO: A genetically modified autologous CD34+ cell enriched population that contains hematopoietic stem cells transduced with lentiviral vector encoding the A-T87Q-globin gene.

Forward-Looking Statements

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the companys financial condition, results of operations, as well as statements regarding the plans for regulatory submissions and commercialization for ZYNTEGLO and the companys product candidates, including anticipated regulatory milestones, the execution of the companys commercial launch plans, planned clinical studies, as well as the companys intentions regarding the timing for providing further updates on the development and commercialization of ZYNTEGLO and the companys product candidates. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated in our ongoing or future clinical trials; the risk of cessation or delay of any of the ongoing or planned clinical studies and/or our development of our product candidates; the risk that the current or planned clinical trials of our product candidates will be insufficient to support regulatory submissions or marketing approval in the United States and European Union; the risk that regulatory authorities will require additional information regarding our product candidates, resulting in delay to our anticipated timelines for regulatory submissions, including our applications for marketing approval; the risk that we will encounter challenges in the commercial launch of ZYNTEGLO in the European Union, including in managing our complex supply chain for the delivery of drug product, in the adoption of value-based payment models, or in obtaining sufficient coverage or reimbursement for our products; the risk that our collaborations, including the collaborations with Bristol-Myers Squibb and Forty Seven, will not continue or will not be successful; and the risk that any one or more of our product candidates, will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

bluebird bio, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except per share data)(unaudited)

For the three months endedDecember 31,

For the year endedDecember 31,

2019

2018

2019

2018

Revenue:

Collaboration revenue

$ 7,159

$ 18,382

$ 36,469

$ 52,353

License and royalty revenue

2,838

861

8,205

2,226

Total revenues

9,997

19,243

44,674

54,579

Operating expenses:

Research and development

161,821

119,722

582,413

448,589

Selling, general and administrative

76,202

53,508

271,362

174,129

Cost of license and royalty revenue

1,073

818

2,978

885

Change in fair value of contingent consideration

1,435

2,156

2,747

2,999

Total operating expenses

240,531

176,204

859,500

626,602

Loss from operations

(230,534)

(156,961)

(814,826)

(572,023)

Interest income, net

6,855

6,209

34,761

14,624

Other (expense) income, net

535

1,916

(10,088)

1,961

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bluebird bio Reports Fourth Quarter and Full Year 2019 Financial Results and Highlights Operational Progress - Yahoo Finance

Studies by researchers at University of South Florida Health (USF Health) Morsani College of Medicine have found that a protein known as -arrestin2 increases the accumulation of the neurotoxic tau tangles that cause several forms of dementia, by interfering with the process that cells use to remove excess tau from the brain. The studies demonstrated that an oligomerized form of -arrestin2, but not monomeric -arrestin2, disrupted the process of autophagy, which would normally act to help rid cells of malformed proteins like disease-causing tau.

Encouragingly, in vivo studies showed that blocking -arrestin2 oligomerization suppressed disease-causing tau in a mouse model that develops a form of human frontotemporal lobar degeneration (FTLD) with dementia, a form of neurodegeneration that is characterized by tau accumulation and the formation of neurofibrillary tangles. Our research could lead to a new strategy to block tau pathology in FTLD, Alzheimers disease, and other related dementias, which ultimately destroys cognitive abilities such as reasoning, behavior, language, and memory, said Jung-A (Alexa) Woo, PhD, an assistant professor of molecular pharmacology and physiology and an investigator at the USF Health Byrd Alzheimers Center. Woo is lead author of the teams published paper in theProceedings of the National Academy of Sciences(PNAS), which is titled, -arrestin2 oligomers impair the clearance of pathological tau and increase tau aggregates.

FTLD, which is also called frontotemporal dementia, is second only to Alzheimers disease (AD) as the leading cause of dementia. This aggressive form of dementia is typically earlier onset, in people aged 4565, and is characterized by atrophy of the front or side regions of the brain, or both. The two primary hallmarks of Alzheimers disease are clumps of amyloid-beta (A) protein fragments known as amyloid plaques, and the tangles of tau protein. Abnormal accumulations of both proteins are needed to drive the death neurons in Alzheimers, although recent research suggests that tau accumulation appears to be required for the toxic effects of A in AD, and correlates better with cognitive dysfunction than A. Indeed, tauopathy correlates significantly better than A with cognitive deficits in AD, the team noted, and drugs targeting A have been disappointing as a treatment.

Like Alzheimers disease, FTLD displays an accumulation of tau, which results in the formation of tau-laden neurofibrillary tangles that destroy synaptic communication between neurons, eventually killing the brain cells. There is no specific treatment or cure for FTLD. However, in contrast with AD, A aggregation is absent in the FTLD brain, in which the key feature of neurodegeneration appears to be the excessive tau accumulation, known as tauopathy. In contrast to AD, where amyloid is an integral part of the tangle, there is no accumulation of A in FTLD neurons , the authors noted.

Previous studies have pointed to an association between G protein-coupled receptors (GPCRs) and AD pathogenesis, and have linked the activation of several, diverse GPCRs with A and/or tau pathogenesis in animal models. While it isnt clear how these very different GPCRs can impact on A and tau pathogenesis, and neurodegeneration in AD, one potential commonality among the receptors is their interaction with arrestins, the researchers noted. Interestingly, previous studies have shown that one of the family of -arrestin proteins known as -arrestin2, is increased in AD brains, and genetic studies have shown that endogenous -arrestin2 promotes A production and deposition, linking -arrestin2 to A pathogenesis. Despite this evidence, the authors acknowledged, prior to the current work, however, it was not known whether, or how, -arrestin2 pathogenically impinges on tauopathy and neurodegeneration in AD, or in FTLD where there is no accumulation of A. As Woo commented, Studying FTLD gave us that window to study a key feature of both types of dementias, without the confusion of any A component.

-arrestin2 in its monomeric form is mostly known for its ability to regulate receptors, but -arrestin2 can also form multiple interconnecting units, called oligomers, and the function of -arrestin2 oligomers is not well understood. While the monomeric form was the basis for the laboratorys initial studies examining tau and its relationship with neurotransmission and receptors, Woo said, we soon became transfixed on these oligomers of -arrestin2.

The teams studies confirmed the presence of elevated -arrestin2 levels, both in cells from the brains of TFLD-tau patients, and in a mouse model. This model expresses disease-associated tau in neurons, and displays FTLD-like pathophysiology and behavior and, like FTLD in humans, doesnt accumulate A.

The researchers also found that -arrestin2 acts to increase tau stability via scaffolding potein:protein interactions. Their results indicated that when -arrestin2 is overexpressed, tau levels also increase, suggesting a maladaptive feedback cycle that exacerbates disease-causing tau. As the authors commented, the data suggested that increased tau increases -arrestin2, which in turn acts to further potentiate tau-mediated events by stabilizing the protein, thus indicative of a vicious positive pathogenic feedback cycle.

To determine the effects of reducing -arrestin2 levels, the team crossed a mouse model of early tauopathy with genetically modified mice in which the -arrestin2 gene was inactivated. They demonstrated that genetic knockdown of -arrestin2 also reduced tauopathy, synaptic dysfunction, and the loss of nerve cells and their connections in the brain. Importantly, experiments confirmed that it was oligomerized -arrestin2, and not the proteins monomeric form, which was associated with increased tau. By blocking -arrestin2 molecules from binding together to create oligomerized forms of the protein, the investigators demonstrated that pathogenic tau significantly decreased when only monomeric -arrestin2, which does bind to receptors, was present.

Further experiments indicated that oligomerized -arrestin2 increases tau by impeding the ability of cargo protein p62 to help selectively degrade excess tau in the brain. In effect, this reduces the efficiency of the autophagy process that would otherwise clear toxic tau. The resulting accumulation of tau clogs up the neurons. Blocking -arrestin2 oligomerization also suppressed disease-causing tau in the mouse model that develops human tauopathy with signs of dementia.

Specifically, our results indicate that -arrestin2 oligomers increase tau levels by blocking the self-interaction of p62, an initial step essential in p62-mediated autophagy flux, the team commented. Genetic reduction or ablation of -arrestin2 significantly decreased sarkosyl-insoluble tau and mitigated tauopathy in vivo. Furthermore, -arrestin2 mutants incapable of forming oligomersactually reduced insoluble tau.

It has always been puzzling why the brain cannot clear accumulating tau, said Stephen B. Liggett, MD, senior author and professor of medicine and medical engineering at the USF Health Morsani College of Medicine. It appears that an incidental interaction between -arrestin2 and the tau clearance mechanism occurs, leading to these dementias. -arrestin2 itself is not harmful, but this unanticipated interplay appears to be the basis for this mystery We also noted that decreasing -arrestin2 by gene therapy had no apparent side effects, but such a reduction was enough to open the tau clearance mechanism to full throttle, erasing the tau tangles like an eraser. This is something the field has been looking foran intervention that does no harm and reverses the disease.

The results point to a potential therapeutic strategy for tauopathies such as FTLD, based on partial inhibition of -arrestin2 oligomerization. For gene therapy of human FTLD-tau, mutants with a somewhat decreased capacity for such inhibition might be desirable, so that some levels of the oligomer are present to carry out other functions Similarly, small molecule inhibitors of -arrestin2 oligomerization, given for treatment or prevention of FTLD-tau, could be designed to spare complete loss of the oligomer in the cell, they suggested. Based on our findings, the effects of inhibiting -arrestin2 oligomerization would be expected to not only inhibit the development of new tau tangles, but also to clear existing tau accumulations due to this mechanism of enhancing tau clearance.

This treatment strategy could be both preventative for at-risk individuals and those with only mild cognitive impairment, and therapeutic in patients with evident FTLD-tau, by decreasing existing tau tangles. Beyond tauopathy, it is conceivable that this strategy could also prove to be beneficial in other neurodegenerative diseases bearing proteinopathies that are cleared via p62, the scientists concluded.

This study identifies beta-arrestin2 as a key culprit in the progressive accumulation of tau in brains of dementia patients, added co-author David Kang, PhD, professor of molecular medicine and director of basic research for the Byrd Alzheimers Center. It also clearly illustrates an innovative proof-of-concept strategy to therapeutically reduce pathological tau by specifically targeting beta-arrestin oligomerization.

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Protein that Prevents Tau Clearance Linked to AD and Other Tau Tangle Proteinopathies - Clinical OMICs News

The Global Gene Therapy Market is expected to grow from USD 1,636.49 Million in 2018 to USD 6,436.64 Million by the end of 2025 at a Compound Annual Growth Rate (CAGR) of 21.60%.

The Gene Therapy Market research presents a study by combining primary as well as secondary research. The report gives insights on the key factors concerned with generating and limiting Gene Therapy market growth.

Additionally, the report also studies competitive developments, such as mergers and acquisitions, new partnerships, new contracts, and new product developments in the global Gene Therapy market. The past trends and future prospects included in this report makes it highly comprehensible for the analysis of the market. Moreover, the latest trends, product portfolio, demographics, geographical segmentation, and regulatory framework of the Gene Therapy market have also been included in the study.

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Gene Therapy Market Segment by Manufacturers includes: Achieve Life Sciences, Inc., Adaptimmune, Bluebird bio, Inc., Gilead, Merck & Co., Inc, Abeona Therapeutics, Inc.,, AGTC, Audentes Therapeutics, Biogen, Editas Medicine, Novartis, Orchard Therapeutics, and Spark Therapeutics.

On the basis of Type, the Global Gene Therapy Market is studied across Antigen Gene Therapy, Cancer Gene Therapy, Cytokine Gene Therapy, Suicide Gene Therapy, and Tumor Suppressor Gene Therapy.

On the basis of Vector Type, the Global Gene Therapy Market is studied across Non-viral Vectors and Viral Vectors.

On the basis of Application, the Global Gene Therapy Market is studied across Cardiovascular Diseases, Genetic Diseases, Infectious Diseases, Neurological Diseases, and Oncological Disorders.

Global Gene Therapy market report covers all the major participants and the retailers will be in conscious of the development factors, market barriers & threats, and the opportunities that the market will offer in the near future. The report also features the historical revenue of the market; industry trends, market volume, and consumption in order to gain perceptions about the political and technical environment of the Gene Therapy market share.

This report focuses on the Gene Therapy in Global market, especially in

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The report gives detailed analysis in terms of qualitative and quantitative data pertaining to the projected potential opportunities that influence markets growth for the forecast period. With a major focus on the key elements and segments of the global Gene Therapy market that might affect the growth prospects of the market, making it a highly informative document.

Major Points covered in this Report:

Market Segmentation:

Regional market analysis

The content of the study subjects includes a total of 15 chapters:

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About Us:We, Regal Intelligence, aim to change the dynamics of market research backed by quality data. Our analysts validate data with exclusive qualitative and analytics driven intelligence. We meticulously plan our research process and execute in order to explore the potential market for getting insightful details. Our prime focus is to provide reliable data based on public surveys using data analytics techniques. If you have come here, you might be interested in highly reliable data driven market insights for your product/service,reach us here 24/7.

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Gene Therapy Market to Witness Considerable Growth Owing to Extensive Demand & Rise in Industrialization by 2025 - Galus Australis

TEL AVIV, Israel, Feb. 20, 2020 (GLOBE NEWSWIRE) -- VBL Therapeutics (Nasdaq: VBLT) today announced the launch of a phase 2 clinical trial of VB-111 in combination with nivolumab (Opdivo), an immune checkpoint inhibitor, in the treatment of metastatic colorectal cancer. The National Cancer Institute (NCI) will serve as the Investigational New Drug (IND) sponsor for this study and the IND application has been approved by the U.S. Food and Drug Administration (FDA). This new study will investigate if priming with VB-111 can drive immune cells into the tumor and turn the colorectal tumor from immunologically cold to hot. The addition of nivolumab to VB-111 may further boost the anti-tumor immune response.

This phase 2 study is part of our strategy to broaden the potential indications for VB-111 and to explore its activity as part of combination therapies, said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics. We look forward to collaborating with NCI on this clinical trial, as we continue to generate data which adds to our understanding of VB-111s mechanism of action and therapeutic potential. We were particularly encouraged by results in ovarian cancer demonstrating the recruitment of infiltrating T cells into a tumor following treatment with VB-111, turning the tumor hot. This important finding suggests that VB-111 may be applied to other cold tumors, in which checkpoint inhibitors show limited or no efficacy, including colorectal cancer, for which there remains a major unmet need.

VBL and the NCI have entered into a Cooperative Research and Development Agreement (CRADA) under the direction of Tim F. Greten, M.D., Deputy Branch Chief & Senior Investigator of the Thoracic and GI Malignancies Branch (TGMB) and Co-Director of the NCI Center for Cancer Research (CCR) Liver Cancer Program. The goal of this open-label, single-arm phase 2 study is to evaluate VB-111 in combination with an anti-PD-1 inhibitor, nivolumab, in patients with metastatic colorectal cancer. In addition to safety and tolerability, this study will evaluate efficacy endpoints including Best Overall Response, as well as immunological and histologic readouts from tumor biopsies. For additional information refer to https://clinicaltrials.gov/show/NCT04166383.

For patients interested in enrolling in this clinical study, please contact NCIs toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the Web site: https://trials.cancer.gov

About VBLVascular Biogenics Ltd., operating as VBL Therapeutics, is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class treatments for cancer. VBLs lead oncology product candidate, ofranergene obadenovec (VB-111), is a first-in-class, targeted anti-cancer gene-therapy agent that is being developed to treat a wide range of solid tumors. It is conveniently administered as an IV infusion once every two months. It has been observed to be well-tolerated in >300 cancer patients and demonstrated activity signals in a VBL-sponsored all comers phase 1 trial as well as in three VBL-sponsored tumor-specific phase 2 studies. Ofranergene obadenovec is currently being studied in a VBL-sponsored phase 3 potential registration trial for platinum-resistant ovarian cancer.

Forward Looking StatementsThis press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as anticipate, believe, could, estimate, expect, goal, intend, look forward to, may, plan, potential, predict, project, should, will, would and similar expressions. These forward-looking statements include, but are not limited to, statements regarding our programs, including VB-111, including their clinical development, such as the timing of clinical trials and expected announcement of data, therapeutic potential and clinical results, and our financial position and cash runway. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, the risk that historical clinical trial results may not be predictive of future trial results, that our financial resources do not last for as long as anticipated, and that we may not realize the expected benefits of our intellectual property protection. A further list and description of these risks, uncertainties and other risks can be found in our regulatory filings with the U.S. Securities and Exchange Commission, including in our annual report on Form 20-F for the year ended December 31, 2018, and subsequent filings with the SEC. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. VBL Therapeutics undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

INVESTOR CONTACT:

Michael RiceLifeSci Advisorsmrice@lifesciadvisors.com(646) 597-6979

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VBL Therapeutics Announces the Launch of a New Clinical Trial of VB-111 Combined with the Checkpoint Inhibitor, Nivolumab, in Metastatic Colorectal...

Viral Vector and Plasmid DNA Manufacturing Market

Facts and Factors Market Researchhas published a new report titled Viral Vector and Plasmid DNA Manufacturing Market By Product (Viral Vectors and Plasmid), By End-User (Biopharmaceutical Companies and Research Institutes), and By Application (Gene & Cancer Therapies, Formulation Development, Viral Infections, and Immunotherapy): Global Industry Perspective, Comprehensive Analysis, and Forecast, 2018 2027. According to the report, the globalviral vector and plasmid DNA manufacturing marketwas valued at approximately USD 418 million in 2018 and is expected to reach a value of around USD 2,237 million by 2027, at a CAGR of around 20.5 % between 2019 and 2027.

Viral vectors are altered viruses that are utilized for inserting genetic material into a cell that can be manipulated for the purpose of healing. These viral vectors prevent the new gene from getting degraded through the delivery of gene castle in the targeted cell. The latter makes use of the new gene to carry out its function. Various kinds of viral vectors include adenoviruses, lentiviruses, and adeno-associated viruses.

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Plasmid DNA gene is utilized for the purpose of cloning, transferring, and manipulating the gene. The key qualities of plasmid include easy working with self-replicating and stability. They are mainly utilized for understanding the gene function and examining RNAs and other genetic material. Plasmid DNA is sectored into conjugative plasmids and non-conjugative plasmids.

Growing occurrence of chronic ailments to drive the market trends

A prominent rise in the aging population prone to chronic disorders along with an increase in incidences of chronic diseases is likely to upsurge the growth of viral vector and plasmid DNA manufacturing industry over the forecast timeline. Moreover, gene therapy offers major treatment facilities for chronic ailments like cancer, inherited diseases, and viral infections.

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Furthermore, the rise in the allocation of funds by private firms on research activities is predicted to drive the market expansion over the forecast timespan. Apart from this, manufacturers are implementing new techniques such as cell line culture development, expression systems, and cell culture system for effectively handling activities related to viral-based vector development. All these factors will upsurge market growth during the forecast period. Nonetheless, the risk of mutagenesis & other obstructions in gene therapy as well as huge costs associated with gene treatment will put brakes on the growth of the market over the forecast period.

Gene & Cancer therapies segment to dominate the application landscape over the forecast period

The growth of the segment is attributed to the rise in the number of gene & cancer therapy subjects along with rapid clinical growth. Apart from this, viral vectors are used for developing gene and T-cell therapies and this will further steer the segmental growth.

Research Institutes to contribute majorly towards the overall market revenue by 2027

The growth of the research institutes segment is attributed to the rise in the research & development activities for launching new therapies to treat chronic ailments like cancer.

North America to dominate the overall regional market growth in terms of revenue by 2027

The growth of the market in the region over the forecast period is due to large-scale government assistance for carrying research activities along with the presence of biopharmaceutical firms in North America. The U.S. is likely to be the regional revenue driver during the forecast timeline.

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Some of the key players in the viral vector and plasmid DNA manufacturing business include Kaneka Corporation (Eurogentec), Cobra Biologics, VGXI, Inc., DNA manufacturing market include Lonza, FUJIFILM Diosynth Biotechnologies Inc., Genzyme Corporation, Vigene Biosciences Inc., Brammer Bio, Oxford Gene Technology, SIRION Biotech GmbH, FinVector Vision Therapies, VIROVEK, Novasep, SPARK THERAPEUTICS, INC., ALDEVRON, and General Electric Company (GE Healthcare).

This report segments the viral vector and plasmid DNA manufacturing market as follows:

Global Viral Vector and Plasmid DNA ManufacturingMarket: By Product Segment Analysis

Global Viral Vector and Plasmid DNA ManufacturingMarket: By End-User Segment Analysis

Global Viral Vector and Plasmid DNA ManufacturingMarket: ByApplicationSegment Analysis

GlobalViral Vector and Plasmid DNA ManufacturingMarket: Regional Segment Analysis

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Global Viral Vector and Plasmid DNA Manufacturing Market to be Worth $2,237 Million by 2027 | CAGR 20.50% - Global Newspaper 24

A PHOTOGRAPHY exhibition showcasing ground-breaking NHS research taking place across the Thames Valley has been launched in Oxford.

TitledThe Body Unlocked: How Research is Changing Lives, it features life-sized photographs of people who have taken part in studies, researchers at work and microscopic images of cells and bacteria.

Images include surgeons preparing a pioneering gene therapy injection for vision loss, dogs smelling urine to detect cancer, a close-up of cells responsible for controlling blood sugar and a virtual reality headset to treat mental illnesses.

The exhibition can be seen for the next two months at Oxfords Covered Market, in the windows of a unit opposite Wicked Chocolate.

ALSO READ: Scientists working on a coronavirus vaccine in Oxford

Among those featured in the exhibition are dementia study participants Barry and Enid Reeves, of Abingdon, who have been married for 70 years.

The couple, both 91, volunteered for the study at Oxford Health NHS Foundation Trust after Mrs Reeves was diagnosed with Alzheimers disease in 2016. Her husband said: Weve become closer as a consequence of her diagnosis because I have become her carer now. The study is not for our benefit particularly, we took part to help others.

In 2018/19, there were 1,930 studies involving 39,129 participants at Oxford University Hospitals NHS Foundation Trust, which manages the John Radcliffe Hospital, Churchill Hospital and Nuffield Orthopaedic Centre in Oxford and Banburys Horton General Hospital.

Professor Keith Channon, director of research and development at the trust, said: Oxford is one of the UKs leading centres for healthcare research, often leading the world in specialties as diverse as neuroscience, cancer, cardiology, diabetes or surgery and delivering improvements in diagnosis and treatment for NHS patients.

ALSO READ: Scientists to share latest dementia research at open day

That research, and the ability to push forward our knowledge of different health conditions, is critically dependent on the participation of many thousands of patients and members of the public from across the region.

We hope that this exhibition, which showcases examples of the ground-breaking research that takes place here, highlights the contributions of patients and members of the public and encourages them to get involved in research studies.

After the Covered Market, the exhibition will travel around the Thames Valley to be displayed at other venues. To find out more visit thebodyunlocked.info.

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Photo exhibition at Covered Market showcases science research - Oxford Mail

Newark, NJ, Feb. 20, 2020 (GLOBE NEWSWIRE) -- As per the report published by Fior Markets, theglobal veterinary x-ray market is expected to grow from USD 651.07 Million in 2017 to USD 1,167.47 Million by 2025 at a CAGR of 7.81% during the forecast period from 2018-2025.

Radiology systems are the most preferred diagnostic tools a veterinarian uses to diagnose diseases in animals. It contains of diagnostic medical descriptions including ultrasound, magnetic resonance tomography, magnetic resonance imaging and atomic imaging. This is a non-invasive way to diagnose the disease. It is a painless procedure, however, animals are often anesthetized to reduce anxiety and stress during the procedure. The rise in the number of pets and the increase in awareness about the well-being of pets is driving the growth of this sector. According to the American Pet Products Association, in 2016, American families had approximately 35% of cats and 44% of dogs, making them around 85.8 million cats and 78 million dogs owned by the United States

The global market for veterinary X-rays is expected to grow rapidly during the forecast period, due to the increasing incidence of animal bone diseases, the increasing number of pets around the world, and the increase in the number of veterinary practitioners worldwide, as it is the main factor driving the market. The high cost of veterinary X-ray tools and the shortage of skilled veterinary technicians may limit market growth. However, high levels of pet insurance may boost future market opportunities.

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Key players operating in the global veterinary X-ray market are IDEXX Laboratories, Fujifilm, Onex Corporation, Agfa-Gevaert Group, Sound Technologies, Sedecal, Examion, Canon, DRE Veterinary, Heska Corporation, Fovea, Clearvet, Control-X Medical, Allpro Imaging, Vetel Diagnostics, Pixxgen and Konica Minolta among others. To enhance their market position in the global veterinary X-ray market, the key players are now focusing on adopting the strategies such as recent developments, product innovation, joint venture, mergers & acquisitions, collaborations, and partnership. Major firms are increasingly investing on research and development activities and development of newer products.

Computed radiography systems is dominating the segment and was valued around USD 286.44 Million in 2017

The technology segment is classified into computed radiography systems segment, direct radiography systems and film-based radiography systems. Computed radiography systems is dominating the segment and was valued around USD 286.44 Million in 2017. Increasing demand for affordable digital X-ray equipment and benefits offered by CR systems over other technologies are contributing for the growth of the segment.

The digital X-rays segment held the largest share of around 56.31% in 2017

Type section includes digital X-rays and analog X-rays. The digital X-rays segment held the largest share of around 56.31% in 2017. X-ray systems offer various benefits over analog systems, which include less costly, improved efficiency, and patient-centric imaging are some of the factors driving the growth of the segment.

The Stationary X-Ray Systems segment is dominated and expected to witness the highest market share of 56 % in the forecast period

The segment is classified into stationary x-ray systems and portable x-ray systems. The stationary x-ray systems is dominated and expected to witness the highest market share of 56% in the forecast period. While new technology advancement and rising use of portable x-ray systems are boosting this segment.

The small companion animals segment is dominated and is expected to held largest share of 61.17% in 2017

Animal type segment includes small companion animals and large animals. The small companion animals segment is dominated and is expected to held largest share of 61.17% in 2017. Increased adoption of pets, growing companionship and demand of highly accurate diagnostic solutions are boosting the growth of the segment.

The orthopedic & trauma segment is dominating and was valued around USD 214.83 million in 2017

Application segment is bifurcated into orthopedics & trauma, dental applications, oncology and other applications. Orthopedic & trauma segment is dominating and was valued around USD 214.83 million in 2017 due to increase in injuries among animals and availability of animal care facilities are contributing to the growth of the segment.

The veterinary hospitals & academic institutes segment is anticipated to grow with the highest CAGR of 9.14% in the forecast period

End user section includes veterinary hospitals & academic institutes and veterinary clinics. The veterinary hospitals & academic institutes segment is anticipated to grow with the highest CAGR of 9.14% in the forecast period. The growth can be accredited to developments in technologies for cost-effective, fast and precise diagnostic tools for animal healthcare.

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Regional Segment Analysis of the Veterinary X-ray market

The regions analysed for the market include North America, Europe, South America, Asia Pacific, and Middle East and Africa. North America region captured the largest share of global veterinary X-ray market and was valued in USD 318.99 Million in 2017 whereas Asia pacific is expected to attain the lucrative growth in the forecast period. North America region is expected to dominate the market due to pet adoption coupled with increasing healthcare expenditure and increase in R&D with growing demand for veterinary equipment. Asia pacific is expected to register the highest growth in the forecast period owing to growing demand for veterinary products and availability of low-cost animal health products are anticipated to drive the growth. Figured radiography and film-based radiography are inexpensive in this region as compared to industrialised regions.

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The global veterinary x-ray market is analysed on the basis of value (USD Million). All the segments have been analyzed on global, regional and country basis. The study includes the analysis of more than 30 countries for each segment. The report offers an in-depth analysis of driving factors, opportunities, restraints, and challenges for gaining the key insight of the market. The study includes porters five forces model, attractiveness analysis, raw material analysis, supply, demand analysis, competitor position grid analysis, distribution and marketing channels analysis.

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Global Veterinary X-ray Market is Expected to Reach USD 1,167.47 Million by 2025 : Fior Markets - GlobeNewswire

Global CNS Gene Therapy Market From PMRs Viewpoint

Decorated with a team of 300+ analysts, PMR Insights serves each and every requirement of the clients while preparing market reports. With digital intelligence solutions, we offer actionable insights to our customers that help them in overcoming market challenges. Our dedicated team of professionals perform an extensive survey for gathering accurate information associated with the market.

PMR, in its latest business report elaborates the current situation of the global CNS Gene Therapy market in terms of volume (x units), value (Mn/Bn USD), production, and consumption. The report scrutinizes the market into various segments, end uses, regions and players on the basis of demand pattern, and future prospect.

In this CNS Gene Therapy market study, the following years are considered to project the market footprint:

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On the basis of product type, the global CNS Gene Therapy market report covers the key segments,

key players and product offerings

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The CNS Gene Therapy market research addresses the following queries:

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CNS Gene Therapy market players Player 1, Player 2, Player 3, and Player 4, among others represent the global CNS Gene Therapy market. The market study depicts an extensive analysis of all the players running in the CNS Gene Therapy market report based on distribution channels, local network, innovative launches, industrial penetration, production methods, and revenue generation. Further, the market strategies, and mergers & acquisitions associated with the players are enclosed in the CNS Gene Therapy market report.

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CNS Gene Therapy Market Growth Factors, Applications, Regional Analysis, Key Players and Forecasts by 2026 - Jewish Life News

GlobalSandhoff disease treatment marketis growing at a steady CAGR in the forecast period of 2019-2026. The report contains data of the base year 2018 and historic year 2017. This rise in market value can be attributed to the orphan drug designation to novel drugs, along with the increasing investment of biotechnology and pharmaceutical industries in R&D.

The key market players in the Sandhoff disease treatment market areIntrabio, Axovant Gene Therapies Ltd among others

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With the market info provided in the Sandhoff Disease Treatment Market report, it has become easy to gain global perspective for the international business. Focus groups and in-depth interviews are included for qualitative analysis whereas customer survey and analysis of secondary data has been carried out under quantitative analysis. This market analysis report acts as a very significant constituent of business strategy. It is a definite study of the Healthcare industry which explains what the market definition, classifications, applications, engagements, and global industry trends are. Sandhoff Disease Treatment Market business document proves to be a sure aspect to help grow the business.

Market Definition: Global Sandhoff Disease Treatment Market

Sandhoff diseaseis also known as Beta-hexosaminidase-beta-subunit deficiency is a fatal pediatric lysosomal storage genetic disorder characterized by progressively destruction of neuron in the brain and spinal cord. It is caused by defects in HEXB gene which is responsible for regulation of vital enzyme called beta-hexosaminidase, as a result of accumulation of lipid called G2 gangliosides. This ongoing accumulation of lipid affects the function of the nerve cells and causes other neurological problem.

Segmentation:Global Sandhoff Disease Treatment Market

Sandhoff Disease Treatment Market : By Types

Sandhoff Disease Treatment Market : ByTherapy

Sandhoff Disease Treatment Market : By Treatment

Sandhoff Disease Treatment Market : By Drugs

Sandhoff Disease Treatment Market : ByRoute of Administration

Sandhoff Disease Treatment Market : By Distribution Channel

Sandhoff Disease Treatment Market : By End-Users

Sandhoff Disease Treatment Market : By Geography

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Key Developments in the Sandhoff Disease Treatment Market

Sandhoff Disease Treatment Market Drivers

Sandhoff Disease Treatment Market Restraints

Sandhoff Disease Treatment Market : Competitive Analysis

Global Sandhoff disease treatment market is highly fragmented and the major players have used various strategies such as new product launches, expansions, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of Sandhoff disease treatment for Global, Europe, North America, Asia-Pacific, South America and Middle East & Africa.

Opportunities in the Sandhoff Disease Treatment Market :-

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Sandhoff Disease Treatment Market 2020-2026 Boosting the Growth Worldwide || Leading Players Intrabio, Axovant Gene Therapies Ltd - News Times

Genetic test results dont add much, if anything, to the risk factor predictions about who will develop cardiovascular disease, according to two studies published in this weeks JAMA.

The study results, while far from the final word, may dent further dent the reputation of genetic testing and give ammunition to skeptics who believe its not ready for clinical use. Payers and providers taking on financial risk may have another reason to tap the brakes.

The findings of both these articles lend further support to the lack of meaningful improvement in risk stratification for CAD [coronary artery disease] in different populations of middle-aged individuals of European ancestry when genome-wide risk scores are added to pooled cohort equations, says an accompanying editorial, which acknowledged that the utility of the tests in a younger or more diverse population remains an open question.

One of the studies used a polygenic risk score developed from a case-control study about 16,000 CAD cases with matched controls. The researchers, most of whom are at the Imperial College Londons School of Public Health, then applied it to a 350,000 individuals from the UK Biobank, 6,272 of whom had a heart attack or some other CAD event during a median follow-up period of eight years. When the polygenic risk score for CAD was used, the predicted risk changes by less than 1% for nearly 80% of the participants. At a risk threshold of 7.5%, 526 of the 6,272 (8.4%) were correctly reclassified to the higher risk category but 240 (4%) were incorrectly moved to a lower risk category. Among the 346,388 noncases, more individuals were incorrectly moved up to a high-risk category than correctly moved down to a lower one (6,723 vs. 5,284) when the polygenic risk score was used.

Lead author Joshua Elliott and his colleagues characterized the number of people meaningfully changing risk category as relatively small and noted the worse reclassification among the noncases.

The other study used data from the 4,847 adults in the Atherosclerosis Risk in Communities study and 2,390 people participating in the Multi-Ethnic Study of Atherosclerosis. The research team, led by Jonathan D. Mosley at Vanderbilt, tested how the addition of a polygenic risk affected prediction of CHD events (heart attacks, silent infarctions, revascularization procedures) over a 10-year period. They found that the testing did not significantly improve classification accuracy in either study and, furthermore, among those who developed CHD the reclassification were incorrect about 80% of the time.

Mosley and his colleagues noted that their findings are in keeping with the frequent mismatch between statistical association and predictive performance for risk biomarkers. They noted that the odds ratio associated with being in the top 5% of the polygenic risk score (about 4) is similar to other biomarkers like C-reactive protein and homocysteine that have been shown to have similarly modest predictive utility.

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JAMA Studies: Genetic Tests for Heart Disease Don't Have Much Predictive Power - Managed Healthcare Executive

The Global Genetic Testing Market is valued at 11.8 billion USD in 2018 and is expected to grow at a CAGR of 11.9% between 2019 and 2025. Rapid industrialization, rising demand for the Genetic Testing, and brisk technological advancements are expected to fuel the market growth during the forecast years.

The global genetic testing market is majorly driven by the importance of early disease diagnosis and prevention, growing need for personalized medicine, increasing application of genetic testing in oncology and increasing awareness on the importance of prognosis and predictive screening. The market is affected by the high costs involved in the genetic testing development and lack of skilled professionals.

Promoting awareness through the government is one of the major factors driving the genetic testing market globally. The government is taking certain initiatives on launching a large number of PGx tests & drugs, controlling the increasing level of genetic disorders, and integrating advanced technologies to meet the needs of patients.

The global Genetic Testing market is deeply analyzed by Market Research Report in a thorough and eclectic research study. The coherent and systematic format of the report allows clients, researchers, stakeholders, and company officials to comprehend the entire market structure.

The report covers several vital market facets that could influence, hinder, or drive market growth momentum. Also, competition in the global Genetic Testing market is evaluated in the report alongside crucial market segments industry environment, and prominent market competitors.

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It also employs diverse analytical tools including Porter's Five Forces Analysis, SWOT Analysis, and Maturity analysis to dig deep into the Genetic Testing market's competitive advantages, various threats, and the existing stage of the market. The report also studies the historical and present events in the Genetic Testing industry in order to provide authentic estimates that will help clients in operating their business accordingly.

The global Genetic Testing market report further hints at market opportunities and challenges, which can be converted into substantial business gains. Potential market threats, risks, uncertainties, and obstacles are also discovered in the report, which can slash the intensity of losses poised to encounter in the near future.

Competitive Scenario of the Global Genetic Testing Market:

The report further enlightens an in-depth analysis of robust Genetic Testing manufacturers/companies and their performance in the market to provide acute knowledge of the competitive intensity of the market. It also studies their pursuits such as product research, development, innovation, and technology adoptions that help players in delivering better fit products in the global Genetic Testing industry.

Their strategic moves were analyzed in the report, including mergers, ventures, amalgamations, acquisitions, product launches, and brand promotion.

Valuable insights into companies' gross margin, Genetic Testing sales volume, profit margin, revenue, growth rate, serving segments, a pricing structure to facilitate clients to intuit the strengths, weaknesses, and market position of their rivals. It also explores their manufacturing base, production facility, volume, capacity, raw material sources, key raw materials, distribution networks, global presence, value chain, effective technologies, equipment, and import-export practices are also covered in the report that provides insightful acumen to understand how leading players are operating their business.

Obtain Detailed Comprehension of the Global Genetic Testing Market

The global Genetic Testing market has been divided into several crucial market segments such as types, applications, regions, end-users, and technology. The report provides concise delineation of each segment considering current demand, revenue, sales, and growth forecasts.

The analysis drives market players to select appropriate market segments and precisely intuit the actual target market size. It also includes a detailed rundown of major regions including North America, Europe, South America, the Middle East & Africa, and the Asia Pacific.

Genetic Testing Market Segmentation by Type:

Genetic Testing Market Segmentation by Application:

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Global Genetic Testing Market projected to gain maximum revenue and share during the forecast period scrutinized in the new analysis - WhaTech...

The announcement by 23andMe, a company that sells home DNA testing kits, that it has sold the rights to a promising new anti-inflammatory drug to a Spanish pharmaceutical company is cause for celebration. The collected health data of 23andMes millions of customers have potentially produced a medical advance the first of its kind. But a few weeks later the same company announced that it was laying off workers amid a shrinking market that its CEO put down to the publics concerns about privacy.

These two developments are linked, because the most intimate data we can provide about ourselves our genetic make-up is already being harvested for ends we arent aware of and cant always control. Some of them, such as better medicines, are desirable, but some of them should worry us.

Launched in Silicon Valley in 2007, 23andMe offers genetic tests direct-to-consumer (DTC) that is, independently of any healthcare system. The company collects genetic information about people, as well as information about their health, behaviour and much more besides. This allows it to identify links between certain genes and, say, a disease, and then through its therapeutics division to develop drugs that interfere with the action of disease-causing genes.

Companies such as 23andMe have proliferated over the past decade, feeding peoples hunger to know who and where they come from, and what diseases their genes might predispose them to. Over that time, it has gradually become clear that the main source of revenue for at least some of these companies comes from selling the data on to third parties.

Some DTC companies, such as 23andMe, are transparent about the sharing of data. When you sign its contract, you are asked if you consent to your data being used for research, and roughly 80% of 23andMes customers do. Other companies are less forthcoming. A 2016 survey showed that only a third of the 86 companies then offering genetic testing services online explained to customers how their data would be used.

The trouble is, a health tech company is not a doctor. It doesnt take the Hippocratic oath, and the patient or customer is not the person whose wellbeing it is most concerned about. It is not obliged to talk you through its terms and conditions, and it could change these at any time though in some jurisdictions this may void your consent. You can also withdraw your consent at any time, but that withdrawal generally takes time to come into effect, and in the meantime your data may have been passed on after which it is harder to get it back. Erasing it entirely is harder still.

And what rights do the customers have over the product developed from their data? DTC companies are far from the only ones collecting sensitive data about you. National health systems, health insurers and, increasingly, social media providers are too. Its already being used in research designed to improve our health and wellbeing, and there is a legitimate question to be asked about compensation. 23andMe, for example, asks its customers to waive all claims to a share of the profits arising from such research. But given those profits could be substantial as evidenced by the interest of big pharma shouldnt the company be paying us for our data, rather than charging us to be tested? There are echoes of Henrietta Lacks here, the African-American woman whose cells became a workhorse of biomedical research after she underwent a biopsy in 1951, and who was never compensated (nor did she give her consent, but that was allowed under US law at the time).

The larger issue, though, is that with all of these databases there is ambiguity about who has access to them, and for what purposes. Besides pharmaceutical companies, others who might want such access include insurance companies, individuals involved in paternity or inheritance disputes, and law enforcement agencies. 23andMe states that it does not grant access to the police, but other companies such as FamilyTreeDNA boasts that it does. A suspect accused of being Californias notorious Golden State Killer was finally arrested in 2018 after investigators matched a DNA sample from a crime scene to the results of DTC testing uploaded on to a public genealogy site by a relative of his. Government-run biobanks have also granted access to police. This was how a conviction was secured against Swedish foreign minister Anna Lindhs assassin in 2004. And experts speculate that in future, biological data could be used for identifying terrorist suspects, tracking military personnel, and the rationing of treatment in overstretched health systems.

National legislation varies widely across Europe, with respect to DTC genetic testing. France and Germany essentially ban it, unless done under medical supervision and consumers can be fined for ordering tests outside a clinical setting, while Luxembourg and Poland allow it with minimal restrictions though, of course, any restrictions are difficult to police for tests bought online. The UK is somewhere in the middle, allowing the tests but insisting on informed consent. The European Unions General Data Protection Regulation (GDPR), which came into effect in 2018, imposes strict requirements on secondary use of data, and it applies to any company in any jurisdiction that targets EU-based individuals for goods or services. Those individuals strip away their own GDPR protection, however, when they contact foreign companies that dont explicitly target them. The UK recently signalled that it will not remain aligned with the GDPR after the Brexit transition period.

These are the privacy concerns that may be behind layoffs, not only at 23andMe, but also at other DTC companies, and that we need to resolve urgently to avoid the pitfalls of genetic testingwhile realising its undoubted promise. In the meantime, we should all start reading the small print.

Laura Spinney is a science journalist, novelist and author

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Your DNA is a valuable asset, so why give it to ancestry websites for free? - The Guardian

Any way you look at it,Invitae (NYSE:NVTA)is smoking hot right now. The stock soared 46% last year and is up more than 60% so far in 2020.

But Invitae's sizzle fizzled at least somewhat after the medical genetics company announced its fiscal 2019 fourth-quarter and full-year results following the market close on Wednesday. Here are the highlights from Invitae's Q4 update.

Image source: Getty Images.

Invitae's revenue jumped 46% year over year in the fourth quarter to $66.3 million. That's the good news. The bad news is that this result fell short of the average analyst Q4 revenue estimate of $68.14 million.

The company reported a net loss of $76.9 million, or $0.79 per share, based ongenerally accepted accounting principles (GAAP). This trended in the wrong direction from the net loss of $29.8 million, or $0.40 per share, posted in the prior-year period.

Invitae announced an adjusted net loss in Q4 of $61.3 million, or $0.63 per share. While this loss was much wider than the adjusted net loss of $31.4 million, or $0.42 per share, recorded in the same quarter of 2018, it was a little better than the consensus Wall Street estimate of a Q4 net loss of $0.65 per share.

CEO Sean George attributed his company's strong revenue growth to several factors. He noted that Invitae expanded its customer base and saw strong reorder rates among new accounts. George also said that the company "made it easier to access our testing, both through traditional payers and via unique partnership programs."

George had predicted over 500,000accessioned samples for full-year 2019 in his comments during Invitae's Q3 conference call in November. But Invitae reported only 482,000 accessioned samples for the year, with the Q4 total sample count of 148,000 coming in lower than expected.

Accessioned samples are the key metric the company uses. The term refers to DNA samples that have been accepted into Invitae's labs and tracked in its system (as opposed to a sample that is collected at a physician's office but not sent to the lab).

Other key developments in the fourth quarter included Invitae's announcement in November that it plans to acquireClear Genetics, a leading developer of software for providing genetic services. The company also announced an initiative with BioMarin Pharmaceuticalto provide genetic testing at no cost to patients with signs or symptoms of skeletal dysplasias, a group of rare bone and joint disorders.

Invitae expects that more than 725,000 samples will be accessioned in full-year 2020. The company projects revenue of over $330 million for the year, up more than 50% from 2019.

Sean George said: "We enter 2020 with momentum and a unique business model that we believe is well positioned to deliver genetics-informed healthcare to patients. As we continue to scale our business, we are confident our approach and the investments we are making will further strengthen our ability to bring affordable, accessible genetic information to billions of people worldwide."

But Invitae is a growth stock with a market cap that can't be justified on its current revenue. It's still not profitable. As a result, any bump in the road is likely to cause the stock to fall. The Q4 update appears to be just such a bump, with shares sinking around 9% in after-hours trading.

Link:
Why Invitae's Q4 Results Failed to Wow Investors - Motley Fool

SEATTLE Morgen White has always wondered what her biological father would be like. She grew up only knowing him as "Donor #893". That changed last year when the genetic testing site 23 & Me connected them.

"Donor #893" was Spokane's Ryan Johnson and he reached out to Morgen and her mother Liz White. The Ballard teen got to meet Johnson, his wife and 3 children and has spent the last year building a relationship.

Morgen says she's been connected to at least 9 other half-siblings, all from the same donor, and loves having so many people that care about and support her. She first wrote about meeting Ryan as part of her internship with KUOW Radioactive Youth Media program.

Segment Producer Suzie Wiley. Watch New Day Northwest 11 AM weekdays on KING 5and streaming live on KING5.com.Contact New Day.

More:
Connected through genetic testing, Ballard teen meets her sperm donor - KING5.com

Are you genetically predisposed to some diseases? Do you carry genetic mutations that can impact the health of your child? A debit card-sized IndiGenome card, recently unveiled by the government, will help you find the answers if your genetic information is captured in a database that India's umbrella research organisation - the Council of Scientific and Industrial Research (CSIR) - is building. Once your genome is sequenced from your blood sample and added to this database, the card can be used to read the information embedded in your genes, just as your debit card is used to generate a financial transaction statement from your bank's database.

Well, the card is not the key. Genome sequencing - or mapping the pattern of the basic building block of every living cell - is. A genome contains all of a living being's genetic material (simply put, the genome is divided into chromosomes, chromosomes contain genes, and genes are made of DNA). Each genome has approximately 3.2 billion DNA base pairs, and the way they are arranged, or variations and mutations in their pattern, can provide clues about the individual's health or ill health, inherited or acquired. Already, 1,008 individuals, chosen to represent India's social, ethnic and geographic diversity, have been issued such cards. Over 280 doctors in 70 institutions have been trained to make sense of such data. A CSIR institute, the Institute of Genomics and Integrative Biology (IGIB) - which is spearheading the Genomics for Public Health in India, also called IndiGen project - is planning to enrol 20,000 Indians for whole genome sequencing in the next couple of years to build a larger database. The data will be important for building the knowhow, baseline data and indigenous capacity in the emerging

area of precision medicine. IndiGen will have applications in a number of areas, including faster and more efficient diagnosis of rare diseases. The other benefits are cost-effective genetic tests, carrier screening applications for expectant couples, enabling efficient diagnosis of heritable cancers and pharmacogenetic tests to prevent adverse drug reactions.

In fact, IGIB leads two other programmes - Genomics for Understanding Rare Diseases India Alliance (GUaRDIAN) Network and Genomics and other Omics tools for Enabling Medical Decision (GOMED), led by Dr Mohammed Faruq, to see that the genome database and genetic screening leads to development of cost effective diagnostic tools and tests that are licensed out to private and public medical institutions.

The world over, fall in cost for genome sequencing (a reason for which is increase in computing power) is leading to path-breaking applications spanning the entire spectrum of healthcare - diagnosis to treatment and drug development to prevention and wellness - and unrelated fields such as agriculture, animal productivity, environment, sports and many more. Consider this: CSIR took six months to sequence the genomes of 1,008 Indians. Seventeen years ago, a global initiative led by the US National Academy of Sciences, had taken 12 years, and spent $3 billion, to complete the sequencing of the first human genome. Today, sequencing a person's genome does not cost more than $1,000. In fact, Sam Santosh, Chairman of MedGenome Labs, a private venture, says he can sequence a complete human genome in his Bengaluru lab for $500-600.

The Industry

The catalyst for the IndiGen project was advent of Next Generation Sequencing (NGS) in the last decade or so. (NGS helps an entire human genome to be sequenced in a day. The previous Sanger sequencing technology used to take over a decade.) The technology is being used by both IGIB and MedGenome for high-throughput sequencing, i.e. sequencing hundreds of thousands of genes in one go.

IndiGen is a good start but there are countries that are much ahead. Genomics England, a public-private partnership between the UK government and world's biggest NGS sequencing machine maker, Illumina, has completed sequencing of 1,00,000 genomes of British citizens comprising a mix of cancer patients, rare disorder patients and healthy people. A new agreement for sequencing of 3,00,000 genomes, with an option to increase it to 5,00,000 over the next five years, was signed by the two partners on January 13. "Countries such as Estonia and Iceland are attempting to sequence every single citizen and link the data with their health schemes. The US has decided to do it for every single rare disorder patient," says Praveen Gupta, Managing Director & Founder, Premas Life Sciences - the authorised partner of US-based Illumina in India.

"The global high-throughput genomics industry will be in the range of $10-12 billion. With an estimated 25-30 per cent annual growth, it is expected to become a $25-30 billion market in the next three-four years," he says. Premas sells tools (reagents, platforms, software, training) to labs that do genetic testing in India. With 90 per cent market share, it drives NGS technology in India, too. "The high-throughput genomics market in India, including reagents, instruments and services, will be about Rs 500 crore. Approximately 50,000 samples must be reaching India's clinical (service) market on an annual basis," says Gupta.

Dr Sridhar Sivasubbu and Dr Vinod Scaria, IGIB scientists at the forefront of the IndiGen programme, say genome sequencing is just one piece of the initiative. IGIB has two other programmes - Genomics for Understanding Rare Diseases India Alliance (GUaRDIAN) Network and Genomics and Other Omics Tools for Enabling Medical Decision (GOMED) - to ensure their genome database and genetic screening lead to development of cost-effective diagnostic tools and tests that can be licensed out to private and public healthcare institutions. "GUaRDIAN focuses on rare diseases. Given that we are a billion-plus people, even the rarest of the rare diseases is found in a few lakh people. So, this programme caters to 70 million people living with some genetic disease. We find technological solutions for these 7,000-odd diseases and partner with a network of 280 clinicians across 70-odd institutions to offer our solutions," says Sivasubbu.

"Patients and their families connect with us through the GUaRDIAN network. We sequence their genes to find the mutation, and once we find it, we go back to their communities with a cost-effective test to identify that mutation. You just have to look for that single mutation in others, and that's cost-effective," says Scaria. Instead of whole genome sequencing, which costs between Rs 50,000 and Rs 1,00,000, a single assay developed by IGIB through these programmes costs Rs 2,000. The team led by Sivasubbu and Scaria has developed 180 tests for 180 genes and transferred the technology to private diagnostic labs. The institute itself has catered to about 10,000 patients and carried about 25,000 tests in the last two years. "We have entered into partnerships with about a dozen companies. The format of the collaboration depends on the business models they follow," says Sivasubbu.

Premas Life Sciences

The authorised partner of US-based Illumina in India provides tools (reagents, platforms, software, training and troubleshooting) to labs engaged in genetic testing in India. With 90 per cent market share, it drives the New Generation Sequencing technology in India

It works in areas other than healthcare, too. For example, Tagtaste, an online platform for food professionals, uses the company's services to understand the genomics of taste. It has customers and partners such as Pepsico, Coca Cola, Nestle and ITC

Dr Lal PathLabs

The company has licensed diagnostic tests for 27 conditions from Institute of Genomics and Integrative Biology (IGIB)

Has a portfolio of more than 200 different types of tests

It is active in fields like rep- roductive health, cancer di- agnosis, pharmacogenomics

Medgenome Labs

The Bengaluru-based player considers itself as the private sector avatar of IGIB. It offers not just genetic tests but also carries out research. It has collaborated with Singapore's Nanyang Technological University to sequence 1,00,000 whole genomes from Asia. The Genome Asia project has already completed sequencing 10,000 whole genomes, of which about 8,000 are from India

MedGenomes research associates recently sequenced and analysed the genome of the Cobra snake. The findings, published in Nature, suggest the possibility of developing a new method of producing anti-venom completely in the lab.

Lifecell International

The company is in the genetic testing space. It has tied up with IGIB and offers tests ranging from basic screening (prenatal screening, newborn screening, etc) to high-end ones based on NGS. It tests more than 50,000 patient samples every month

Mahajan Imaging

The company has set up a new R&D wing to focus on cutting-edge scientific and clinical research and help radiology and genomics companies develop world-class clinically relevant products. The idea is to integrate imaging and genomic data

Trivitron Healthcare

The Chennai-based chain wants to develop tools using genomic data that can work on conventional platforms. It is talking to IGIB and trying to get its knowhow for manufacture of products for sale to pathology labs

The Private Hand

Dr Lal PathLabs, a pathology lab chain with big plans in the genetic testing space, has an entire department for such tests. "We offer tests of all levels - Karyotyping, which looks at the macro level, Microarrays, which offer intermediate resolution, and NGS, used to elucidate the DNA sequence at the micro level. The fields we are active in include prenatal reproductive health, cancer diagnosis and pharmacogenomics (study of how genes affect a person's response to drugs). We have more than 200 tests and conduct around 300 tests per day," says Dr Vandana Lal, Executive Director, Dr Lal PathLabs. The company has licensed tests for 27 conditions from IGIB. "The imported technology is expensive. The idea to partner with CSIR labs is to bring these cutting-edge technologies to Indian masses at a reasonable cost," says Dr Lal.

Lifecell International is another player in the genetic testing space that has tied up IGIB. "We offer tests ranging from basic screening (prenatal screening, newborn screening, etc.) to high-end ones based on NGS. We test more than 50,000 samples a month. PCR-based tests range from Rs 2,000-5,000 whereas tests based on NGS and those involving sequencing of large parts of the genome can cost upwards of Rs 20,000," says Ishaan Khanna, CEO, Biobank & Diagnostics, Lifecell. He believes the IndiGen database will help in development of better analysis and interpretation tools. "Our focus is on developing rapid genome testing for children in NICU (Neonatal ICU) and similar other scenarios where doctors need clear actionable results in the shortest possible time. IndiGen provides the right mix of Indian genome database," he says.

But not every partnership is for access to cost-effective tests. Mahajan Imaging, a medical imaging chain, has set up a Centre for Advanced Research in Imaging, Neuroscience and Genomics to focus on research and helping radiology and genomics companies develop clinically relevant products. The idea is to integrate imaging and genomic data. "We started the project six months ago and are among the first imaging companies to get into genomics. In the next three-five years, it will be possible for an AI algorithm to look at the radiology image and give genomic readings on it," says Vidur Mahajan, Associate Director, Mahajan Imaging.

Chennai-based Trivitron Healthcare sees in IndiGene data an opportunity to develop multiple testing platforms. It wants to develop tools using genomic data that can work on conventional platforms. "There are almost 1,00,000 pathology labs in India. Hardly 500-1,000 must be doing genetic testing. Companies like ours are talking to IGIB and trying to get the knowhow to manufacture products for a larger population," says Jameel Ahmad Khan, Head, R&D, Trivitron. "IGIB will develop the knowhow, provide proof of concept, and we will convert it into a product which pathology labs without highly trained manpower can also run," he says.

Bengaluru-based Medgenome Labs considers itself a private sector avatar of IGIB, perhaps even a couple of years ahead in research and development. The company not only does genetic tests but also carries out research. It has collaborated with Singapore's Nanyang Technological University to sequence 1,00,000 whole genomes from Asia. The Genome Asia project has already completed sequencing of 10,000 whole genomes, of which about 8,000 are from India. On December 4, international journal Nature published the initial findings from the project - genetic variation, population structure, disease associations, etc., from a whole-genome sequencing reference dataset of 1,739 individuals of 219 population groups and 64 countries across Asia. "We sequence a person's genes and other relevant parts of the genome for specific mutations to understand what is causing the disease and specific drugs and dosage the person will respond to. We also help pharmaceutical companies understand genomes and discover new drug targets and biomarkers," says Sam Santosh, Chairman, MedGenome. With about 120 sales people, the company claims it is generating samples from around 10,000 clinicians across the country. "We were the first to enter the market. In that sense, we created the market, and would be having 60-65 per cent market share. The sequencing market must be in the range of $70-75 million," says Santosh. The company expects its diagnostic business to touch $100 million in four years. Interestingly, MedGenome's research associates recently sequenced and analysed the genome of Cobra snake. The findings, published in Nature, suggest the possibility of developing a new method of producing anti-venom completely in the lab.

Other Sectors

Illumina's India partner Premas Life Sciences is not selling its next generation sequencers only to healthcare firms. Gupta says it has more than 200 installations in India alone. "Anything which is living has a DNA nucleic acid and can be sequenced. We have a mass research market and practically every institute has the sequencer. Somebody will be working on cow, somebody on rice, a third institute on some bacteria," says Gupta.

IGIB researchers Dr Sridhar Sivasubbu and Dr Vinod Scaria vouch for this. The institute is getting requests, including partnership offers, from non-medical players. Tagtaste, an online platform for food professionals, wants to understand the genomics of taste. "In a lighter vein, you could say that the efficiency of a professional wine taster depends on his genes," says Scaria. With customers and partners such as Pepsico, Coca Cola, Nestle and ITC, and a clientele that includes chefs of global hotel chains, taste is serious business. "The point is, if a person is paying Rs 3,000 for a curry or Rs 5,000 for a soup, you better get the taste right," says Scaria. IGIB also works with Adam's Genetics for R&D and product development in the area of fitness. "One of the companies works in the cricket industry. Each player can be genetically tested for performance and food intake because not all muscles have the same size and some people gain weight, some don't gain muscle mass, while some may be more prone to injury. Genetic tests can find out who is prone to injury, or whether weightlifting is the right exercise for a player or not," says Sivasubbu.

The Future

Indians are 17 per cent of the world's population. But only 0.2 per cent genomic data is from the Indian population. This is one area where India can lead. We have so many diseases, and if we can provide the genetic design, the world can develop diagnostics and therapies. "We can create ideas. We didn't invent computers but we created the IT industry. In the same way, we didn't invent genomic sequences but tomorrow we can create a genome informatics economy," says Premas' Gupta.

There are other possibilities, too. "A lot of pundits say that in the next five-six years, 15 per cent of the world's population will be whole genome sequenced. If I require 100 GB data for a genome sequence, for 1.5 billion people, 25-30 exabytes of data will be needed. The entire data content on YouTube, globally, is 0.8 exabytes. Imagine the kind of data generation and analytics possibilities we are talking about," says Gupta. "We need people to analyse this data. If we can take the lead and train our manpower, we can move the world, we can create a new industry which can lead for the next 20 years just the way the IT industry did," he adds. Incidentally, Gupta claims that TCS has already bought Illumina's sequencing platform. So has WIPRO. It seems IT companies are already sensing an opportunity.

Sivasubbu says it took India 10 years to scale up from sequencing one genome to 1,000 genomes. "In the next decade, it may be a million."

@joecmathew

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The Gene Business - Business Today