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Archive for the ‘Gene Therapy Research’ Category

Gene Therapy Saves Puppies From A Fatal DiseaseAnd Maybe Us Next – Vocativ

For decades, some unluckydog lovers have welcomeda bundle of barking joy into their homes, only to see them perish from a mysterious disease mere weeks after their birth. The pups seemingly healthy muscles had literally wasted away in front of their owners eyes until they could no longer stand and breathe.

It wasnt until 2010 that a French research team isolated the genetic cause of this specific muscle-wasting disease in a group of Labrador Retrievers; these dogs were suffering from a single mutation that left them unable to produce an essential protein known asmyotubularin.Whats more, it was the exact kind of mutation and disease also long found in male human babies, too. That made the researchers wonder if these unfortunate puppiescould help us study the disease and even someday find a way to saveboth pets and people.

Now, years down the road, it appearsthey were right, thanks to a cutting-edgegene therapy treatment.

An international group of researchers, including some from the original French team, gathered together 10-week-old puppies with the mutation to take part in a randomized controlled trial. The dogs who were given a treatment that repaired their defectivemyotubularingene avoided the crippling muscle degeneration that killed the placebo-treated dogs by week 17. And by the ninth month of study, the saved puppies muscle and neurological function continued to match readings from healthy dogs, particularly forthose that got the highest doses.

The findings, building on an earlier proof-of-concept study of dogs and mice by the researchers, signal that a scaled-up treatment could save the lives of boys with the same sort of genetic flaw.

I believe that the dog study will be about as close as we will ever get to a human study, senior author Dr. Martin Childers of the University of Washington told Vocativ in an email. Because we found evidence that the gene therapy product spread throughout the entire skeletal musculature of adult dogs after a single infusion, it seems reasonable to expect a similar result in human patients.

Gene therapy has received plenty of attention for its potential to treat otherwise irreparable DNA defects, but according to the researchers, theres been little focus on bone- and muscle-relatedgenetic disorders. The condition treated in the current study, called x-linked myotubular myopathy, affects around one in every 50,000 boys, with most sufferers living no more than a few years. And though theres no true tally of how often it affects dogs, case reports of similar-sounding diseases have been published stretching back decades.

There will undoubtedly be hurdles to climb before the treatment Childers and his team developed, or a similar one, can be tested in people, Childers said. It is always possible that humans might respond differently, thus, clinical trials will be conducted with extraordinary care and oversight, he explained. And though the dogs suffered little adverse effects from the therapy delivered via a harmless virus researchers will still have to watch out for any possible toxicity in people.

That said, the treatment offers hope for both man and mutts. The changes seen after a single treatment have lasted for several years in the small sample of dogs the team has raised. So its possible that people wont need repeated doses or they would be infrequent, Childers said a big positive, given how expensive gene therapy is today.

And its also likely that these treatments, within the larger field of regenerative medicine, will find a place for dogs and other animals sooner than it will for people.

Veterinary medicine is ahead of human medicine in some cases with respect to regenerative technologies, Childers said. Stem cell infusions, for example, have been given to pets and horses for more than a decade.

But people may not have to wait so long for the promise of gene therapy either. Childers is hopeful that Audentes Therapeutics, a San Francisco biomedical company hes collaborating with (and which partially funded the current study), will begin their first human trials of a gene therapy treatment for x-linked myotubular myopathy, based on his teams research, later this year.

The teams findings were published earlier this February in Molecular Therapy.

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Gene Therapy Saves Puppies From A Fatal DiseaseAnd Maybe Us Next – Vocativ

Stanford scientists create glow-in-the-dark mice, may advance gene therapies – The Indian Express

By: PTI | Updated: February 20, 2017 6:53 pm Not only did mRNA technique make the mouse glow, it also later ran around, completely unaware of the complex series of events that had just taken place within its body, researchers said. ( Image for representation, Source: Youtube)

Stanford scientists have successfully developed glow-in-the-dark mice using compounds that create proteins responsible for lighting up fireflies, an advance that may pave the way for new gene therapies.

Timothy Blake, a postdoctoral fellow at Stanford University in the US refined compounds that carry instructions for assembling the protein that makes fireflies light up and delivered them into the cells of an anaesthetised mouse.

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Not only did the technique make the mouse glow, it also later woke up and ran around, completely unaware of the complex series of events that had just taken place within its body, researchers said.

This success could mark a significant step forward for gene therapy. It is hard enough getting these protein instructions, called messenger RNA (mRNA), physically into a cell. It is another hurdle altogether for the cell to actually use them to make a protein. If the technique works in people, it could provide a new way of inserting therapeutic proteins into diseased cells.

Its almost a childlike enthusiasm we have for this, said Robert Waymouth, a professor at Stanford. The code for an insect protein is put into an animal and that protein is not only synthesised in the cells but its folded and it becomes fully functional, capable of emitting light, said Waymouth. Although the results are impressive, this technique is remarkably simple and fast. Unlike traditional gene therapy that permanently alters the genetic makeup of the cell, mRNA is short-lived and its effects are temporary.

The transient nature of mRNA transmission opens up special opportunities, such as using these compounds for vaccination or cancer immunotherapy. Gene therapy is a decades-old field of research that usually focuses on modifying DNA, the fundamental genetic code. That modified DNA then produces a modified mRNA, which directs the creation of a modified protein.

Also Read:Gene-editing cell therapy saves two babies from cancer

The current work skips the DNA and instead just delivers the proteins instructions. They used a novel, deceptively straightforward creation, called charge-altering releasable transporters (CARTs). What distinguishes this polycation approach from the others, which often fail, is the others dont change from polycations to anything else, said Paul Wender, professor at Stanford.

Whereas, the ones that were working with will change from polycations to neutral small molecules. That mechanism is really unprecedented, Wender said. As part of their change from polycations to polyneutrals, CARTs biodegrade and are eventually excreted from the body.

One application of this technology is vaccination. At present, vaccines require introducing part of a virus or an inactive virus into the body in order to elicit an immune response. CARTs could potentially cut out the middleman, directly instructing the body to produce its own antigens.

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Stanford scientists create glow-in-the-dark mice, may advance gene therapies – The Indian Express

Global Gene Therapy Technologies, Markets and Companies 2016-2026 – Research and Markets – PR Newswire (press release)

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2015, over 2050 clinical trials have been completed, are ongoing or have been approved worldwide.A breakdown of these trials is shown according to the geographical areas and applications.

The markets for gene therapy are difficult to estimate as there is only one approved gene therapy product and it is marketed in China since 2004. Gene therapy markets are estimated for the years 2016-2026. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright.The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

Profiles of 188 companies involved in developing gene therapy are presented along with 233 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report.

Key Topics Covered:

Part I: Technologies & Markets

1. Introduction

2. Gene Therapy Technologies

3. Clinical Applications of Gene Therapy

4. Gene Therapy of Genetic Disorders

5. Gene Therapy of Cancer

6. Gene Therapy of Neurological Disorders

7. Gene Therapy of Cardiovascular Disorders

8. Gene therapy of viral infections

9. Research, Development and Future of Gene Therapy

10. Regulatory, Safety and Ethical Issues of Gene Therapy

11. Markets for Gene Therapy

12. References

Part II: Companies

13. Companies involved in Gene Therapy

For more information about this report visit http://www.researchandmarkets.com/research/jtwqds/gene_therapy

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Laura Wood, Senior Manager press@researchandmarkets.com

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Global Gene Therapy Technologies, Markets and Companies 2016-2026 – Research and Markets – PR Newswire (press release)

‘Exciting’ new therapy shows promising results for hemophilia … – CTV News

CTVNews.ca Staff Published Friday, February 17, 2017 10:00PM EST Last Updated Friday, February 17, 2017 10:28PM EST

A small gene therapy trial involving several Canadian patients is offering new hope to people living with hemophilia, a rare and potentially fatal genetic disorder.

Hemophilia patients can suffer prolonged or uncontrollable bleeding, even after minor injuries. That’s because they lack blood clotting factors, or proteins.

There are two types of hemophilia, A and B, and both are very rare disorders. Hemophilia A affects an estimated 2,500 Canadians, while hemophilia B affects about 600 Canadians, according to the Canadian Hemophilia Society.

A new gene therapy developed at the Children’s Hospital in Philadelphia has produced very encouraging results. Preliminary research suggests that a single dose of the experimental therapy may help patients with hemophilia B, which involves a deficiency of blood clotting factor IX.

The therapy involves using a gene engineered to replace the faulty one in people with hemophilia. The engineered gene is placed into an inactivated virus and then infused into the liver, where it helps the body produce a clotting factor that prevents bleeding.

“It poses the possibility for a one-time treatment that would bepotentially life-altering for the patient,” Dr. Lindsey George, a hematologist at The Children’s Hospital of Philadelphia, told CTV News.

Scientists found that after just one dose, none of the nine patients involved in the trial suffered any bleeding for up to a year. Although more research and larger studies are needed to confirm the benefits of the therapy, researchers are very encouraged.

“It is very exciting, certainly from my standpoint as a clinical investigator,” Dr. George said.

Dr. Jerry Teitel, the medical director of the Hemophilia Treatment Centre at St. Michael’s Hospital in Toronto, who collaborated with the Philadelphia researchers, called it “a revolutionary therapy.”

The results so far are wonderful, in fact even better than what we had dared to hope,” he said.

Of the nine patients who’ve received the treatment, four are Canadian.

Among them is John Konduros, a 52-year-old bakery owner in Cambridge, Ont. As a lifelong hemophiliac, he has always lived in fear of any bumps, cuts or bruises that could cause internal bleeding, disability — and even death.

“It has probably affected every single part of my life, from being a kid to now,” he told CTV News. “If you ever saw me as a kid, I was never in a group. I was always on the sides.”

Konduros said it was common for him to miss two or three weeks of school if another kid happened to kick him in the leg while they were playing. In one class photo, he is seen with a big bruise under his right eye – another side effect of his condition.

But since Konduros received the experimental treatment about eight months ago, he has not had any dangerous bleeds.

“I’m extremely happy in the sense of massive relief. I feel like I don’t have to be as vigilant or worrisome about everything and anything that’s going on around me,” he said.

So far, the immune systems of two trial patients have reacted to the treatment, but scientists say there were no serious side effects. Konduros has had no problems with the therapy.

“If the doctors wanted me to go down every weekend for more tests to accelerate anything I would say ‘sure’ because the improvement it gives anyone who has hemophilia is huge,” he said.

Dr. Teitel said scientists have “a long way to go” in developing a therapy that can help more hemophilia patients.

“We need to show that in large numbers, the results do hold up,” he said. “We need to show that the results last for a long period of time, not necessarily last a lifetime.”

With files from CTV’s medical specialist Avis Favaro and producer Elizabeth St. Philip

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‘Exciting’ new therapy shows promising results for hemophilia … – CTV News

Cancer Therapy Conference | October 2017 | Baltimore | USA

Sessions and Tracks

Cancer is a class of diseases characterized by out-of-control cell growth. There are more than 100 distinct sorts of cancer and each is ordered by the kind of cell which is first influenced. Malignancy is thought to be one of the main sources of grimness and mortality around the world. More than 575,000 individuals bite the dust of tumor and more than 1.5 million individuals are determined to have disease every year in the US. A restorative expert who hones in the field of cancer and cancer related diseases is an oncologist.

In addition to the multidisciplinary talks, keynote sessions and lectures relevant to cancer science & therapy, the Cancer therapy 2017 is a complete 3 days event with panel discussions, open Q & A to generate a prime learning knowledge between participants.

Scientific Session of the Conference includes:

Cancer Cell Biology

Cancer Metastasis

Cancer Genetics

Tumor & Cancer Immunology

Cancer : Genomics & Metabolomics

Targeted Cancer Therapy

Stem Cell Therapy

Cancer Biomarkers

Cancer Case Reports

Novel Approaches to Cancer Therapeutics

Precision Medicine & Cancer Therapy

Cancer Management & Prevention

Cancer Pharmacology

Organ Specific Cancers

Radiation Oncology

Surgical Oncology

Cancer Drugs

Complementary and Alternative Cancer Treatment

Cancer Clinical Trials

Cancer & Lifestyle

Cancer: Psychological & Social Aspects

Cancer Diagnostics & Diagnostic Market

1. Cancer Cell Biology

Cancerous tumors are threatening, which implies they can spread into, or attack adjacent tissues. What is more, as these tumors develop, some cancer cells can sever and go to distant places in the body through the blood or the lymph framework and shape new tumors a long way from the first tumor. Cancer cells emerge from the body’s own particular tissues. Cancer Cell Biology incorporates the molecular, biochemical and cell-based ways to deal with better comprehend cancer pathogenesis.

2. Cancer Metastasis

Metastasis is the spread of a cancer or other infection from one organ or part of the body to another without being straightforwardly associated with it. At the point when cancer cells split far from a tumor, they can go to different territories of the body through the circulatory system or the lymph framework. The lungs, liver, brain and bones are the most well-known metastasis areas from solid tumors. Treatment and survival is resolved, by regardless of whether a cancer stays confined or spreads to different areas in the body.

3. Cancer Genetics

Cancer is a hereditary sickness and is brought about by specific changes to qualities that control the way our cells work, particularly how they develop and separate. These progressions incorporate transformations in the DNA that makes up our qualities. A few sorts of cancers keep running in specific families, yet most tumors are not unmistakably connected to the qualities we acquire from our folks. Quality changes that begin in a solitary cell throughout a man’s life cause generally malignancies. A few people are hereditarily inclined to building up specific sorts of cancers. These individuals have a higher danger of building up the malady than those in the overall population. Hereditary testing is currently accessible for some inherited cancers. Genetic testing includes a straightforward blood test and might be utilized to get a more exact gauge of your growth hazard. Now and again, Genetic testing should be possible on put away tissue tests from deceased relatives.

4. Tumor & Cancer Immunology

Tumor immunology depicts the cooperation between cells of the invulnerable framework with tumor cells. Understanding these interactions is imperative for the improvement of new treatments for tumor treatment. In many people the resistant framework perceives and disposes of Tumor cells. Cancer immunology is a branch of immunology that reviews collaborations between the resistant framework and cancer cells (likewise called tumors or malignancies). It is a field of research that plans to find cancer immunotherapies to treat and retard movement of the disease. The immune response, including the recognition of cancer-specific antigens, forms the basis of targeted therapy, (such as vaccines and antibody therapies) and tumor marker-based diagnostic tests.

5. Cancer genomics & metabolomics

Cancer genomics is the study of the totality of DNA sequence and gene expression differences between tumor cells and normal host cells. It aims to understand the genetic basis of tumor cell proliferation and the evolution of the cancer genome under mutation and selection by the body environment, the immune system and therapeutic interventions. The metabolites within a cell or biological system are being used to analyze cancer metabolism on a system-wide scale, painting a broad picture of the altered pathways and their interactions with each other. Cancer metabolomics involves chemical analysis by a range of analytical platforms through targeted/untargeted approaches. The application of metabolomics towards cancer research has led to a renewed appreciation of metabolism in cancer development and progression.

Tumor cell proliferation

Genomic Studies

Cancer Genome Atlas (TCGA)

Genomics Tools

Metabolic Technologies

Data Interpretations

Metabolomics as Biomarker

6. Targeted Cancer Therapy

Targeted Cancer therapy is a newer type of cancer treatment that uses drugs or other substances to more precisely identify and attack cancer cells, usually while doing little damage to normal cells. Targeted therapy is a growing part of many cancer treatment regimens. Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer. The Drugs work by targeting specific genes or proteins. These genes and proteins are found in cancer cells or in cells related to cancer growth, like blood vessel cells. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells.

Therapeutic Monoclonal Antibodies

Small Molecule Drugs

Tyrosine-kinase inhibitors

Implications of Targeted Therapy

Targeted Cancer Therapy & Health Economics

Hormone Therapies

7. Stem Cell Therapy

Stem Cells and Tumors Cancer Cells also have the characteristic that is associated with normal stems cells. Stem Cell Therapy is used to prevent the disease. The most common stem cells therapy is bone marrow transplantation. Stems cells transplant is used to treat cancers like leukemia, multiple myeloma of lymphoma. Cord Blood Stem and Cancer cord blood contains hematopoietic (blood) stem cell. These cells make different types of cells like red blood cells, white blood cells, Hematopoietic stem cells, purified from bone marrow or blood, have long been used in stem cell treatments for leukemia, blood and bone marrow disorders when chemotherapy is used.

Cancer Stem Cells

Stem Cells and Tumors

Stem Cell Transplantation

Bone Marrow Transplantation

Cord Blood Stem Cells and Cancer

Stem Cell Research

8. Cancer Biomarkers

A cancer biomarker is an element or procedure that indicates the presence of cancer in the body. A biomarker may be any molecule released by the presence of a tumor or a specific indication of the body to the presence of cancer. Cancer biomarkers are usually biological molecules found in blood, other body fluids, or tissues that are a sign of a normal or abnormal process, or of a condition or disease.

Imaging Biomarkers

Clinical Biomarkers

Genetic Biomarkers

Predictive Cancer Biomarkers

Molecular Biomarkers

Cell Free Biomarkers

9. Cancer Case Reports

A case report signifies the detailed report of symptoms, signs, diagnosis, treatment and follow-up of an individual patient of a particular disease. Cancer Case reports have been playing a pivotal role in medical education, providing a structure for case-based learning and implementation throughout the world.

Unexpected/Unusual Conditions

Rare Surgical Condition of a cancer case

Novel Surgical Procedure

Adverse Effects

Innovative in Cancer Surgery

10. Novel Approaches to Cancer Therapeutics

The Normal treatment modalities are associated with severe side effects and high toxicity which in turn lead to low quality of life. This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis. Currently, cancer treatment is a highly dynamic field and significant advances are being made in the development of novel cancer treatment strategies. In contrast to conventional cancer therapeutics, novel approaches such as ligand or receptor based targeting, intracellular drug targeting, gene delivery, cancer stem cell therapy, magnetic drug targeting and ultrasound-mediated drug delivery, have added new modalities for cancer treatment.

Cancer Epigenetics

Molecular Profiling Techniques

New Biologics & Vaccines

Chemical Proteomics

Combination Strategies in Immuno-oncology

Novel Biomarker Discovery

11. Precision Medicine & Cancer Therapy

Precision medicine also known as Personalized Medicine is a phrase that is often used to describe how genetic information about a persons disease is being used to diagnose or treat their disease. The deeper understanding of how cancer forms and grows has ushered in a new era of precision cancer care, where tailored treatments target abnormalities that may be found in each tumors DNA profile. This exciting innovation marks a shift, from traditional treatments designed for the average patient based on their success with a representative sample of people with similar cancers, towards more precise therapies.

Genomics Mutations

Molecular Diagnostics

Non-Genetic Characteristics

Targeted Drug Therapies

Clinical Trials of Personalized Medicine

12. Cancer Management & Prevention

Cancers that are closely linked to certain behaviors are the easiest to prevent. Many complementary health approaches are also found to combat the risks of cancers like, for example, herbal and other dietary supplements, acupuncture, massage and yoga.

Lifestyle changes

Diet & Cancer

Vaccinations

Natural Therapy

Psychological & Social Aspects

13. Cancer Pharmacology

Cancer pharmacology plays a key role in drug development. In both the laboratory and the clinic, cancer pharmacology has had to adapt to the changing face of drug development by establishing experimental models and target orientated approaches.

Tumor Targeting Strategies

Hormonal & Biological Agents

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Cancer Therapy Conference | October 2017 | Baltimore | USA

Glowing mice suggest new gene therapy technique — ScienceDaily – Science Daily

Timothy Blake, a postdoctoral fellow in the Waymouth lab, was hard at work on a fantastical interdisciplinary experiment. He and his fellow researchers were refining compounds that would carry instructions for assembling the protein that makes fireflies light up and deliver them into the cells of an anesthetized mouse. If their technique worked, the mouse would glow in the dark.

Not only did the mouse glow, but it also later woke up and ran around, completely unaware of the complex series of events that had just taken place within its body. Blake said it was the most exciting day of his life.

This success, the topic of a recent paper in Proceedings of the National Academy of Sciences, could mark a significant step forward for gene therapy. It’s hard enough getting these protein instructions, called messenger RNA (mRNA), physically into a cell. It’s another hurdle altogether for the cell to actually use them to make a protein. If the technique works in people, it could provide a new way of inserting therapeutic proteins into diseased cells.

“It’s almost a childlike enthusiasm we have for this,” said chemistry Professor Robert Waymouth. “The code for an insect protein is put into an animal and that protein is not only synthesized in the cells but it’s folded and it becomes fully functional, capable of emitting light.”

Although the results are impressive, this technique is remarkably simple and fast. And unlike traditional gene therapy that permanently alters the genetic makeup of the cell, mRNA is short-lived and its effects are temporary. The transient nature of mRNA transmission opens up special opportunities, such as using these compounds for vaccination or cancer immunotherapy.

Making a protein

Gene therapy is a decades-old field of research that usually focuses on modifying DNA, the fundamental genetic code. That modified DNA then produces a modified mRNA, which directs the creation of a modified protein. The current work skips the DNA and instead just delivers the protein’s instructions.

Previous work has been successful at delivering a different form of RNA — called short interfering RNA, or siRNA — but sending mRNA through a cell membrane is a much bigger problem. While both siRNA and mRNA have many negative charges — so-called polyanions — mRNA is considerably more negatively charged, and therefore more difficult to sneak through the positively charged cell membrane.

What the researchers needed was a positively charged delivery method — a polycation — to complex, protect and shuttle the polyanions. However, this alone would only assure that the mRNA made it through the cell membrane. Once inside, the mRNA needed to detach from the transporter compound in order to make proteins.

The researchers addressed this twofold challenge with a novel, deceptively straightforward creation, which they call charge-altering releasable transporters (CARTs).

“What distinguishes this polycation approach from the others, which often fail, is the others don’t change from polycations to anything else,” said chemistry Professor Paul Wender, co-author of the paper. “Whereas, the ones that we’re working with will change from polycations to neutral small molecules. That mechanism is really unprecedented.”

As part of their change from polycations to polyneutrals, CARTs biodegrade and are eventually excreted from the body.

The power of collaboration

This research was made possible through coordination between the chemists and experts in imaging molecules in live animals, who rarely work together directly. With this partnership, the synthesis, characterization and testing of compounds could take as little as a week.

“We are so fortunate to engage in this kind of collaborative project between chemistry and our clinical colleagues. It allowed us to see our compounds go from very basic building blocks — all the way from chemicals we buy in a bottle — to putting a firefly gene into a mouse,” said Colin McKinlay, a graduate student in the Wender lab and co-lead author of the study.

Not only did this enhanced ability to test and re-test new molecules lead to the discovery of their charge-altering behavior, it allowed for quick optimization of their properties and applications. As different challenges arise in the future, the researchers believe they will be able to respond with the same rapid flexibility.

After showing that the CARTs could deliver a glowing jellyfish protein to cells in a lab dish, the group wanted to find out if they worked in living mice, which was made possible through the expertise of the Contag lab, run by Christopher Contag, professor of pediatrics and of microbiology and immunology. Together, the multidisciplinary team showed that the CARTs could effectively deliver mRNA that produced glowing proteins in the thigh muscle or in the spleen and liver, depending on where the injection was made.

A bright future ahead

The researchers said CARTs could move the field of gene therapy forward dramatically in several directions.

“Gene therapy has been held up as a silver bullet because the idea that you could pick any gene you want is so alluring,” said Jessica Vargas, co-lead author of the study, who was a PhD student in the Wender lab during this research. “With mRNA, there are more limitations because the protein expression is transient, but that opens up other applications where you wouldn’t use other types of gene therapy.”

One especially appropriate application of this technology is vaccination. At present, vaccines require introducing part of a virus or an inactive virus into the body in order to elicit an immune response. CARTs could potentially cut out the middleman, directly instructing the body to produce its own antigens. Once the CART dissolves, the immunity remains without any leftover foreign material present.

The team is also working on applying their technique to another genetic messenger that would produce permanent effects, making it a complementary option to the temporary mRNA therapies. With the progress already made using mRNA and the potential of their ongoing research, they and others could be closer than ever to making individualized therapeutics using a person’s own cells. “Creating a firefly protein in a mouse is amazing but, more than that, this research is part of a new era in medicine,” said Wender.

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Glowing mice suggest new gene therapy technique — ScienceDaily – Science Daily

Gene therapy treats muscle-wasting disease in dogs: Single infusion … – Science Daily

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease. UW Medicine Institute for Stem Cell and Regenerative Medicine scientists are leading the multi-institutional research effort.

The disease arises from a mutation in genes that normally make a protein, called myotubularin, essential for proper muscle function. Puppies with this naturally occurring mutation exhibit several features of babies with the same defective gene. The rare disorder, called myotubular myopathy, or MTM, affects only males. It causes fatal muscle wasting. Both dogs and boys with the disease typically succumb in early life due to breathing difficulties.

For decades, researchers have struggled to find suitable treatments for genetic muscle diseases like this one. Four collaborating research groups in the United States and France found a way to safely replace the disease-causing MTM gene with a healthy gene throughout the entire musculature of affected dogs.

Their most recent findings were published online this week in Molecular Therapy.

Their paper reports that diseased dogs treated with a single infusion of the corrective therapy were indistinguishable from normal animals one year later.

“This regenerative technology allowed dogs that otherwise would have perished to complete restoration of normal health,” said Dr. Martin K. “Casey” Childers, UW Medicine researcher and physician. Childers is a professor of rehabilitation medicine at the University of Washington School of Medicine and co-director of the Institute for Stem Cell and Regenerative Medicine.

Gene therapy holds the promise to treat many inherited diseases. To date, this approach has not been widely translated into treatment of skeletal muscle disorders.

“We report here a gene therapy dose-finding study in a large animal model of a severe muscle disease where a single treatment resulted in dramatic rescue,” said Childers. The findings demonstrate potential application across a wide range of diseases and broadly translate to human studies. The data supports the development of gene therapy clinical trials for myotubular myopathy, the researchers concluded.

UW Medicine researchers David Mack, Melissa Goddard, Jessica Snyder, Matthew Elverman, and Valerie Kelly co-authored the report, “Systemic AAV8-mediated gene therapy drives whole-body correction of myotubular myopathy in dogs.” This study was conducted in collaboration with Harvard University, Medical College of Wisconsin, Virginia Tech, INSERM, and Genethon.

Story Source:

Materials provided by University of Washington Health Sciences/UW Medicine. Original written by Barbara Rodriguez. Note: Content may be edited for style and length.

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Gene therapy treats muscle-wasting disease in dogs: Single infusion … – Science Daily

Penn Orphan Disease Center Partners with Foundation … – Newswise – Newswise (press release)

Newswise PHILADELPHIA — Penn Medicines Orphan Disease Center (ODC) announces a new partnership with FAST (Foundation for Angelman Syndrome Therapeutics) to study gene therapy approaches to treat Angelman syndrome (AS). FAST will provide funding to establish a gene therapy research program led by ODC.

Angelman syndrome is a rare neurological disorder that affects about one in 15,000 people, totaling about 490,000 worldwide. Individuals with AS have balance issues, motor impairment, and seizures, among other symptoms. Typical characteristics are not usually evident at birth, and people with the disorder develop feeding difficulties as infants and delayed development at about six to 12 months. In most cases, AS is not inherited and is often misdiagnosed as autism or cerebral palsy.

The Orphan Disease Center is delighted to launch a new collaboration with FAST on the development of gene therapy for Angelman syndrome, said ODC director James M. Wilson, MD, PhD, who is also a professor of Medicine and Pediatrics in the Perelman School of Medicine at the University of Pennsylvania. Combining ODCs experience in novel therapeutics with the tremendous progress made by FAST and its families, caregivers, and scientists has set the stage for an aggressive and exciting research plan.

Since its inception, ODC has aligned its mission to address the unmet needs of the rare disease community. ODC focuses on making rare disease research a priority and is committed to ensuring that the best science is accessible to the global community and to patients across all populations.

Currently, there are no treatments for AS, which is caused by mutations in the UBE3A gene and the loss of UBE3A protein expression. In the brain, UBE3A is primarily expressed by the maternal copy of the gene through a biological process known as paternal imprinting. UBE3A is an enzyme that targets proteins for removal from the cell, although it is not known how the loss of UBE3A in the brain leads to AS. Developing a gene therapy for AS will focus on replacing this gene in children who are lacking a functional copy.

We are excited to launch a new effort in Angelman syndrome in collaboration with the Angelman community and FAST, said Ashley Winslow, PhD, ODC senior director. Advancements in the understanding of AS make therapeutic approaches like gene therapy a natural fit for treating Angelman syndrome.

All of the board members of FAST are parents who are working toward breakthrough treatments for our children, said FAST chief scientific officer Allyson Berent, DVM, DACVIM. In making a commitment to develop an AS-specific gene therapeutic, Dr. Wilson and his research team further confirm our belief that Angelman syndrome is a curable disorder. To have an accomplished visionary researcher developing a potential gene therapy treatment for AS indicates we are closer than ever to this ultimate goal. Dr. Wilson and the team at Penn have such a successful track record in the field of gene therapy, and we are beyond enthusiastic that, for our children, the time is now.

The Orphan Disease Center is expanding its emphasis on neurodevelopmental disorders, such as AS, and through this effort hopes to leverage expertise across closely related disorders to accelerate therapeutic development.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year. The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital — the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

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Penn Orphan Disease Center Partners with Foundation … – Newswise – Newswise (press release)

In a possible step forward for gene therapy, researchers made mice glow like fireflies – Phys.Org

February 16, 2017 by Taylor Kubota Colin McKinlay and Jessica Vargas are co-lead authors of research that could mark a significant step forward for gene therapy by providing a new way of inserting therapeutic proteins into diseased cells. Credit: L.A. Cicero

Timothy Blake, a postdoctoral fellow in the Waymouth lab, was hard at work on a fantastical interdisciplinary experiment. He and his fellow researchers were refining compounds that would carry instructions for assembling the protein that makes fireflies light up and deliver them into the cells of an anesthetized mouse. If their technique worked, the mouse would glow in the dark.

Not only did the mouse glow, but it also later woke up and ran around, completely unaware of the complex series of events that had just taken place within its body. Blake said it was the most exciting day of his life.

This success, the topic of a recent paper in Proceedings of the National Academy of Sciences, could mark a significant step forward for gene therapy. It’s hard enough getting these protein instructions, called messenger RNA (mRNA), physically into a cell. It’s another hurdle altogether for the cell to actually use them to make a protein. If the technique works in people, it could provide a new way of inserting therapeutic proteins into diseased cells.

“It’s almost a childlike enthusiasm we have for this,” said chemistry Professor Robert Waymouth. “The code for an insect protein is put into an animal and that protein is not only synthesized in the cells but it’s folded and it becomes fully functional, capable of emitting light.”

Although the results are impressive, this technique is remarkably simple and fast. And unlike traditional gene therapy that permanently alters the genetic makeup of the cell, mRNA is short-lived and its effects are temporary. The transient nature of mRNA transmission opens up special opportunities, such as using these compounds for vaccination or cancer immunotherapy.

Making a protein

Gene therapy is a decades-old field of research that usually focuses on modifying DNA, the fundamental genetic code. That modified DNA then produces a modified mRNA, which directs the creation of a modified protein. The current work skips the DNA and instead just delivers the protein’s instructions.

Previous work has been successful at delivering a different form of RNA – called short interfering RNA, or siRNA – but sending mRNA through a cell membrane is a much bigger problem. While both siRNA and mRNA have many negative charges – so-called polyanions – mRNA is considerably more negatively charged, and therefore more difficult to sneak through the positively charged cell membrane.

What the researchers needed was a positively charged delivery method – a polycation – to complex, protect and shuttle the polyanions. However, this alone would only assure that the mRNA made it through the cell membrane. Once inside, the mRNA needed to detach from the transporter compound in order to make proteins.

The researchers addressed this twofold challenge with a novel, deceptively straightforward creation, which they call charge-altering releasable transporters (CARTs).

“What distinguishes this polycation approach from the others, which often fail, is the others don’t change from polycations to anything else,” said chemistry Professor Paul Wender, co-author of the paper. “Whereas, the ones that we’re working with will change from polycations to neutral small molecules. That mechanism is really unprecedented.”

As part of their change from polycations to polyneutrals, CARTs biodegrade and are eventually excreted from the body.

The power of collaboration

This research was made possible through coordination between the chemists and experts in imaging molecules in live animals, who rarely work together directly. With this partnership, the synthesis, characterization and testing of compounds could take as little as a week.

“We are so fortunate to engage in this kind of collaborative project between chemistry and our clinical colleagues. It allowed us to see our compounds go from very basic building blocks – all the way from chemicals we buy in a bottle – to putting a firefly gene into a mouse,” said Colin McKinlay, a graduate student in the Wender lab and co-lead author of the study.

Not only did this enhanced ability to test and re-test new molecules lead to the discovery of their charge-altering behavior, it allowed for quick optimization of their properties and applications. As different challenges arise in the future, the researchers believe they will be able to respond with the same rapid flexibility.

After showing that the CARTs could deliver a glowing jellyfish protein to cells in a lab dish, the group wanted to find out if they worked in living mice, which was made possible through the expertise of the Contag lab, run by Christopher Contag, professor of pediatrics and of microbiology and immunology. Together, the multidisciplinary team showed that the CARTs could effectively deliver mRNA that produced glowing proteins in the thigh muscle or in the spleen and liver, depending on where the injection was made.

A bright future ahead

The researchers said CARTs could move the field of gene therapy forward dramatically in several directions.

“Gene therapy has been held up as a silver bullet because the idea that you could pick any gene you want is so alluring,” said Jessica Vargas, co-lead author of the study, who was a PhD student in the Wender lab during this research. “With mRNA, there are more limitations because the protein expression is transient, but that opens up other applications where you wouldn’t use other types of gene therapy.”

One especially appropriate application of this technology is vaccination. At present, vaccines require introducing part of a virus or an inactive virus into the body in order to elicit an immune response. CARTs could potentially cut out the middleman, directly instructing the body to produce its own antigens. Once the CART dissolves, the immunity remains without any leftover foreign material present.

The team is also working on applying their technique to another genetic messenger that would produce permanent effects, making it a complementary option to the temporary mRNA therapies. With the progress already made using mRNA and the potential of their ongoing research, they and others could be closer than ever to making individualized therapeutics using a person’s own cells. “Creating a firefly protein in a mouse is amazing but, more than that, this research is part of a new era in medicine,” said Wender.

Explore further: Don’t kill the messenger RNA

More information: Colin J. McKinlay et al. Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1614193114

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Gene Therapy Technologies, Markets and Companies 2017 – Research and Markets – Business Wire (press release)

DUBLIN–(BUSINESS WIRE)–Research and Markets has announced the addition of Jain PharmaBiotech’s new report “Gene Therapy – Technologies, Markets and Companies” to their offering.

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2015, over 2050 clinical trials have been completed, are ongoing or have been approved worldwide. A breakdown of these trials is shown according to the geographical areas and applications.

The markets for gene therapy are difficult to estimate as there is only one approved gene therapy product and it is marketed in China since 2004. Gene therapy markets are estimated for the years 2016-2026. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright. The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

Profiles of 188 companies involved in developing gene therapy are presented along with 233 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report.

Key Topics Covered:

Part I: Technologies & Markets

1. Introduction

2. Gene Therapy Technologies

3. Clinical Applications of Gene Therapy

4. Gene Therapy of Genetic Disorders

5. Gene Therapy of Cancer

6. Gene Therapy of Neurological Disorders

7. Gene Therapy of Cardiovascular Disorders

8. Gene therapy of viral infections

9. Research, Development and Future of Gene Therapy

10. Regulatory, Safety and Ethical Issues of Gene Therapy

11. Markets for Gene Therapy

12. References

Part II: Companies

13. Companies involved in Gene Therapy

For more information about this report visit http://www.researchandmarkets.com/research/npn4n6/gene_therapy

The rest is here:
Gene Therapy Technologies, Markets and Companies 2017 – Research and Markets – Business Wire (press release)

Global Gene Therapy Technologies, Markets and Companies 2016-2026 – Research and Markets – PR Newswire UK (press release)

DUBLIN, Feb. 15, 2017 /PRNewswire/ —

Research and Markets has announced the addition of Jain PharmaBiotech’s new report “Gene Therapy – Technologies, Markets and Companies” to their offering.

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors. Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2015, over 2050 clinical trials have been completed, are ongoing or have been approved worldwide.A breakdown of these trials is shown according to the geographical areas and applications.

The markets for gene therapy are difficult to estimate as there is only one approved gene therapy product and it is marketed in China since 2004. Gene therapy markets are estimated for the years 2016-2026. The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright.The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

Profiles of 188 companies involved in developing gene therapy are presented along with 233 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report.

Key Topics Covered:

Part I: Technologies & Markets

1. Introduction

2. Gene Therapy Technologies

3. Clinical Applications of Gene Therapy

4. Gene Therapy of Genetic Disorders

5. Gene Therapy of Cancer

6. Gene Therapy of Neurological Disorders

7. Gene Therapy of Cardiovascular Disorders

8. Gene therapy of viral infections

9. Research, Development and Future of Gene Therapy

10. Regulatory, Safety and Ethical Issues of Gene Therapy

11. Markets for Gene Therapy

12. References

Part II: Companies

13. Companies involved in Gene Therapy

For more information about this report visit http://www.researchandmarkets.com/research/jtwqds/gene_therapy

Media Contact:

Laura Wood, Senior Manager press@researchandmarkets.com

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

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Global Gene Therapy Technologies, Markets and Companies 2016-2026 – Research and Markets – PR Newswire UK (press release)

Gene therapy treats muscle-wasting disease in dogs – Medical Xpress

February 15, 2017 In a study replacing the mutated gene responsible for myotubular myopathy with a healthy gene throughout the entire musculature of affected dogs, researchers observed a relationship between dosage and survival. Credit: Martin Childer lab/UW Medicine

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease. UW Medicine Institute for Stem Cell and Regenerative Medicine scientists are leading the multi-institutional research effort.

The disease arises from a mutation in genes that normally make a protein, called myotubularin, essential for proper muscle function. Puppies with this naturally occurring mutation exhibit several features of babies with the same defective gene. The rare disorder, called myotubular myopathy, or MTM, affects only males. It causes fatal muscle wasting. Both dogs and boys with the disease typically succumb in early life due to breathing difficulties.

For decades, researchers have struggled to find suitable treatments for genetic muscle diseases like this one. Four collaborating research groups in the United States and France found a way to safely replace the disease-causing MTM gene with a healthy gene throughout the entire musculature of affected dogs.

Their most recent findings were published online this week in Molecular Therapy.

Their paper reports that diseased dogs treated with a single infusion of the corrective therapy were indistinguishable from normal animals one year later.

“This regenerative technology allowed dogs that otherwise would have perished to complete restoration of normal health,” said Dr. Martin K. “Casey” Childers, UW Medicine researcher and physician. Childers is a professor of rehabilitation medicine at the University of Washington School of Medicine and co-director of the Institute for Stem Cell and Regenerative Medicine.

Gene therapy holds the promise to treat many inherited diseases. To date, this approach has not been widely translated into treatment of skeletal muscle disorders.

“We report here a gene therapy dose-finding study in a large animal model of a severe muscle disease where a single treatment resulted in dramatic rescue,” said Childers. The findings demonstrate potential application across a wide range of diseases and broadly translate to human studies. The data supports the development of gene therapy clinical trials for myotubular myopathy, the researchers concluded.

UW Medicine researchers David Mack, Melissa Goddard, Jessica Snyder, Matthew Elverman, and Valerie Kelly co-authored the report, “Systemic AAV8-mediated gene therapy drives whole-body correction of myotubular myopathy in dogs.” This study was conducted in collaboration with Harvard University, Medical College of Wisconsin, Virginia Tech, INSERM, and Genethon.

Explore further: Gene therapy leads to robust improvements in animal model of fatal muscle disease

More information: Molecular Therapy, http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(17)30056-4 , DOI: 10.1016/j.ymthe.2017.02.004

Preclinical studies show that gene therapy can improve muscle strength in small- and large-animal models of a fatal congenital pediatric disease known as X-linked myotubular myopathy. The results, appearing in the Jan. 22 …

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Zebrafish with very weak muscles helped scientists decode the elusive genetic mutation responsible for Native American myopathy, a rare, hereditary muscle disease that afflicts Native Americans in North Carolina.

University of Michigan researchers have discovered a new cause of congenital myopathy: a mutation in a previously uncharacterized gene, according to research published this month in the American Journal of Human Genetics.

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease. UW Medicine Institute for Stem Cell and Regenerative …

Purdue University and Indiana University School of Medicine scientists were able to force an epigenetic reaction that turns on and off a gene known to determine the fate of the neural stem cells, a finding that could lead …

Just before Rare Disease Day 2017, a study from the Monell Center and collaborating institutions provides new insight into the causes of trimethylaminura (TMAU), a genetically-transmitted metabolic disorder that leads to …

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A new study shows how errors in a specific gene can cause growth defects associated with a rare type of dwarfism.

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Gene therapy treats muscle-wasting disease in dogs – Medical Xpress

Human genome editing shouldn’t be used for enhancement yet – New Scientist

CRISPR: gene editing made easy

Ella Maru Studio/SPL

By Jessica Hamzelou

While gene editing is already saving lives, for now, the technique shouldnt be used to edit embryos or create changes that will be passed on through the generations. So say the authors of a new report on editing the human genome.

However, such germline editing could be permitted in the future, if properly regulated and with public approval, concludes the report. It was compiled by the Committee on Human Genome Editing, a group of 22 researchers, lawyers and ethicists.

Gene therapy isnt new, but the development of the CRISPR Cas-9 technique has made it much easier to change a genome. The technique enables researchers to specifically target a region of DNA and add or remove genes both a useful tool for research, and a technique that can treat diseases in people.

But gene editing treatments are not without some risk. Theres a chance, for instance, that a therapy will have off-target effects, changing other genes. The risks will depend on the disorder and the treatment, and regulators must weigh up the risks against treatment benefits on a case-by-case basis, the authors say.

The risks are higher when it comes to germline editing. Beyond off-target effects, theres a chance that attempts to perform gene editing on an embryo will create a mosaic of treated and untreated cells. Its the most common problem in mouse studies, says Robin Lovell-Badge of the Francis Crick Institute in London, who co-authored the report.

Lovell-Badge and his colleagues concluded that germline editing could be performed in humans, but only after much more research to minimise the risks and weigh them up against any benefits. Even then, the public must have a say, and any trials must be performed under strict oversight.

The report is also not in favour of gene editing techniques to enhance people, or create designer babies but only for the time being. Its the thing that worries people the most, because it is felt to be unfair, says Lovell-Badge. Its the same as using drugs to cheat.

But the boundary between treatment and enhancement is often blurred. If you were able to lower a persons cholesterol for example, where would the cut-off be? In the future, some aspects of enhancement might be considered acceptable, says Lovell-Badge. We may need to modify aspects of our physiology to adapt to climate change, but thats being speculative, he says. Were not saying it should never be done but not now.

Based on what we already know about genes and health, it might be possible to boost a persons muscle mass, for instance, using gene editing. But for many other features including intelligence hundreds or thousands of genes are involved. Using gene editing to enhance these features isnt currently feasible.

Read more: Why banning CRISPR gene editing would be unnecessarily cautious

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Human genome editing shouldn’t be used for enhancement yet – New Scientist

Lipid nanoparticles for gene therapy — ScienceDaily – Science Daily

25 years have passed since the publication of the first work on solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as a system for delivering drugs. So the European Journal of Pharmaceutics and Biopharmaceutics has prepared a special edition for which it asked the PharmaNanoGene group of the UPV/EHU-University of the Basque Country to produce a piece of work reviewing the application of SLNs and NLCs in gene therapy since the group’s significant contributions made in this area have been included in various international scientific publications.

Lipid nanoparticles (SLNs and NLCs) are regarded as highly promising systems for delivering nucleic acids in gene therapy. Until now, viral systems have been the most effective method for delivering genetic matter but they pose significant safety problems. “Non-viral vectors, including SLNs and NLCs, are less effective but much safer even though their effectiveness has increased significantly in recent years,” pointed out Alicia Rodrguez, Mara ngeles Solins and Ana del Pozo, authors of the article published in the European Journal of Pharmaceutics and Biopharmaceutics.

This review article describes these systems and their main advantages in gene therapy, such as their capacity to protect the gene material against degradation, to facilitate cell and nucleus internalisation and to boost the transfection process. “What is more, the nanoparticles are made up of biocompatible, biodegradable materials, they are easy to produce on a large scale, they can be sterilised and freeze-dried and are very stable both in biological fluids and in storage,” explained the researchers.

This review also includes the main diseases in which lipid nanoparticles are being applied, generally on the preclinical level: degenerative diseases of the retina, infectious diseases, metabolic disorders, and cancer, among others. “At PharmaNanoGene we are working on the design and evaluation of SLNs for treating some of these diseases using gene therapy. We are studying the relationship between formulation factors and the processes involving the intracellular internalisation and disposition of the genetic material that condition the effectiveness of the vectors and which is essential in the optimisation process, and for the first time we have demonstrated the capacity of SLNs to induce the synthesis of a protein following their intravenous administration in mice,” they stressed.

The publication also includes other pieces of work by this UPV/EHU research group on the application of SLNs in the treatment of rare diseases, such as chromosome-X-linked juvenile retinoschisis, a disorder in which the retina becomes destructured due to a deficiency in the protein retinoschisin. “One of the main achievements of our studies in this field has been to demonstrate, also for the first time, the capacity of a non-viral vector to transfect the retina of animals lacking the gene that encodes this protein and partially restore its structure, showing than non-viral gene therapy is a viable, promising therapeutic tool for treating degenerative disorders of the retina,” specified the researchers.

The application of SLNs for treating Fabry disease, a serious, multi-system metabolic disorder of a hereditary nature, has also been studied at PharmaNanoGene. “This is a monogenic disease linked to the X-chromosome which is caused by various gene mutations in the gene that encodes the a-galactosidase A (a-Gal A) enzyme. In cell models of this disease we have demonstrated the capacity of SLNs to induce the synthesis of a-Gal A.” They have also reviewed the application of lipid nanoparticles to the treatment of infectious diseases: “Our work in this field shows that SLNs with RNA interference are capable of inhibiting a replicon of the hepatitis C virus in vitro, which was used as proof-of-concept of the use of SLN-based vectors as a new therapeutic strategy for treating this infection and others related to it.”

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Lipid nanoparticles for gene therapy — ScienceDaily – Science Daily

CRISPR’s breakthrough problem | February 13, 2017 Issue – Vol. 95 … – The Biological SCENE

In brief

In fewer than five years, a gene-editing technology known as CRISPR has revolutionized research. Now, many are wondering if it can do the same for medicine. Several companies are hoping to commercialize CRISPR-based therapies that could potentially offer a permanent fix for a vast array of genetic diseases. But theres a catch: Getting CRISPR into the body, across cell membranes, and into human DNA is no simple feat. Read on to learn how chemists and bioengineers are joining the CRISPR craze to solve gene editings delivery dilemma.

In fewer than five years, an important new gene-editing tool called CRISPR has radically changed the face and pace of biological research. The ability to quickly and cleanly remove and replace stretches of DNA has already inspired thousands of publications featuring the technique and led to the creation of a slew of biotech businesses hoping to capitalize on CRISPR.

CRISPRs power to effortlessly target and tweak any piece of DNA seems limitless. Thomas Barnes is the chief scientific officer of the CRISPR-centered Intellia Therapeutics, whose founders include one of the inventors of CRISPR, Jennifer Doudna. He says there is an ever-growing backlog of well-understood rare genetic conditions with little that people can do about them. Barnes hopes CRISPR will change that.

By tackling genetic disease at its rootsmutations in the DNACRISPR could end thousands of ailments, Barnes and others believe. Multiple research groups and companies are hot on the tracks of unleashing CRISPR on sickle cell disease, hemophilia, cystic fibrosis, Duchenne muscular dystrophy, genetic forms of blindness, and, of course, cancer.

The hype is partly about CRISPRs broad applicability, but CRISPRs true promise is its potential for a one-and-done cure. Changing your DNA is a permanent fix. CRISPRshort for the clustered regularly interspaced short palindromic repeats in the bacterial immune system from which the technology was derivedis a two-part system: a customizable guide RNA and a protein called Cas9. The guide RNA directs Cas9 to any desired segment of DNA for editing. The Cas9 enzyme then cuts the DNA at that precise location, allowing for genes to be turned on or off or for the removal or insertion of DNA.

But editing the DNA of cells in a petri dishor even curing a mouse of a diseaseis one thing; making the hot new technology work in humans is a whole other challenge. Sneaking the gene-editing complex into human cells is no easy task.

It will take some fancy molecular maneuvering to get the bulky Cas9 protein and the negatively charged guide RNA into humans. To work its magic, the unwieldy gene-editing system first needs to get into the body, skirt past the immune system, and infiltrate its target tissue. From there, it must sneak across cell membranes, escape the acidic environment of the cells endosomes to find the nucleus, and then home in on the correct location on the DNA. In other words, CRISPR has a drug delivery problem.

The Cas9 enzyme and the guide RNA composing the CRISPR complex cannot be swallowed in pill form or simply injected into the bloodstream. And a one-size-fits-all package is unlikely to work for every condition, so researchers are eagerly testing old strategies and creating new ones to achieve a CRISPR cure.

David Liu of Harvard University says this delivery dilemma isnt unusual for a new gene-editing technology, but researchers now feel this incredible urgency and excitement because of the promise of using CRISPR for therapeutic applications. Since its inception as a gene-editing tool in 2012, nearly 5,000 papers mentioning CRISPR have been published in PubMed. The CRISPR craze is reeling in polymer chemists, drug delivery designers, and bioengineers all helping move CRISPR from the lab bench to the doctors office.

Ive just never seen any field that progresses at this pace, says Niren Murthy of the University of California, Berkeley, who cofounded a start-up called GenEdit, dedicated to CRISPR delivery, in February 2016. There is nothing comparable to the competitiveness of the CRISPR field, he says.

From a delivery perspective, I am sure there will be all sorts of surprises, says Kathryn Whitehead of Carnegie Mellon University. C&EN spoke with more than 30 academic and industry researchers about CRISPRs delivery dilemma. Some expect success soon. Others are trying to temper expectations, pointing to the historically long time horizon for turning new technologies into treatments. But as Whitehead says, If this is possible, everything changes.

CRISPR gene editing is derived from a primordial immune system in bacteria called clustered regularly interspaced short palindromic repeats. A guide RNA, which is complementary to a target DNA sequence, directs the Cas9 enzyme (light blue) to a specified location for DNA cutting. Some applications require an additional DNA template (not shown) to fill in the cut. Source: Adapted from OriGene Technologies

CRISPR isnt the first gene-editing technology promising to cure thousands of diseases. In fact, multiple studies of treatments developed using older technologies are now under way. Drug delivery guru Daniel Anderson of Massachusetts Institute of Technology points out that one of the most advanced programs is Sangamo Biosciences ongoing clinical trial to remove T cells from patients, edit their DNA to make them resistant to HIV, and reinject the modified cells. So presumably, there are some genome-edited people walking around in California that they helped create, Anderson says.

Sangamo is using an older gene-editing tool called zinc finger nucleases, a complex protein structure designed to bind and cleave a specific region of DNA. And doctors at the Great Ormond Street Hospital in London recently reported using a similar gene-editing technique called TALENs, which also recognizes and cuts precise DNA sequences, to engineer immune cells for a therapy that may have cured two infants of leukemia.

Both technologies have been around for longer than CRISPR has, with zinc-finger-based editing being in the works for more than two decades. They also both suffer from a limitation that has inhibited their widespread adoption: Each is a cumbersome protein complex that needs to be individually engineered for every new DNA target.

CRISPR, meanwhile, is easily adaptable. The Cas9 cutting protein remains the same for all applications, and to make a new edit, researchers need only to switch out the guide RNA. If the DNA sequence that needs editing is known, securing the complementary guide RNA is as easy as clicking Order from a supplier.

When CRISPR came along, everyone knew what to do with it, Intellias Barnes says. People had been going around in a go-kart and you gave them a Ferrari, so away they go.

Jacob Corn of UC Berkeley says cheap and easily customizable guide RNA empowers the democratization of gene editing. Corns lab is one of several using CRISPR to cureat least in isolated cells and micesickle cell disease, where a single-letter DNA mutation stymies the oxygen-ferrying capacity of red blood cells.

Corn envisions a world where patient DNA testing is coupled to CRISPRs customizability, and scientists can easily whip up a fix for problematic genetic mutations. I think that, in the future, well be able to tackle genetic diseases with the same speed we can diagnose them, he says.

Corns dream might not be far off, at least for blood disorders such as sickle cell disease. In that condition, stem cells collected from the blood or bone marrow could be removed from a patient, edited in the lab to correct the DNA typoa process called ex vivo gene editingand then reinjected to proliferate and make a patient healthy.

Editing cells harvested from a patient is relatively straightforward. Researchers commonly use electroporation, a technique that uses an electric pulse to momentarily create pores that allow the Cas9 protein and guide RNA complex to slip inside cells in a dish. This technique has the potential to address hematological disorders and is also being used to beef up immune cells to fight cancers such as leukemia.

Lloyd Klickstein, head of translational medicine for the new indications discovery unit at the Novartis Institutes for BioMedical Research, says, Thus far, the ex vivo technologies are whats been done, and thats what most of the companies are looking to do first, Novartis included.

The concept looks promising on paper, but no one knows how well it will work in humans. Chinese researchers at Sichuan University claimed to be the first to do ex vivo therapy with a handful of people with cancer last year, and University of Pennsylvania researchers are gearing up for a similar clinical trial in Philadelphia, San Francisco, and Houston this year.

Although researchers are excited about the potential to use CRISPR to create therapies from peoples own blood, immune, and stem cells, thousands more genetic conditions affect everything else. For those disorders, CRISPR needs to be delivered like more traditional medicines so it can work its wonders editing DNA inside the body. But the challenge of shuttling CRISPR directly to the diseased tissue, or in vivo gene editing, is so daunting it could stall CRISPRs otherwise rapid advancement.

The first in vivo CRISPR therapy to be tested in humans will likely borrow its delivery vehicle from the world of gene therapy, where hollowed shells of viruses are used to transport genes inside cells and then, in theory, permanently produce a therapeutic protein. Decades of gene therapy research has yielded a reasonably good carrier for genetic material, the adeno-associated virus (AAV). Compared with other viral vehicles, the immune system tends to ignore AAV, and the carrier is able to target specific cell types in the body.

Editas Medicines founding scientific adviser is one of CRISPRs inventors, Feng Zhang of the Broad Institute. Editas is using AAV to deliver CRISPR in monkeys. In this study, CRISPR targets the genetic mutation that causes Leber congenital amaurosis 10, a rare form of progressive childhood blindness. The biotech firm plans to ask FDA for permission to start human studies of the treatment, which must be directly injected into the eye, by the end of this year. We chose that disease because we felt that we could deliver our machinery there, says Charles Albright, chief scientific officer of Editas.

Seokjoong Kim, research director at the South Korea-based gene-editing company ToolGen, is also conducting CRISPR experiments in mice for eye disorders, including age-related macular degeneration and diabetic retinopathy. ToolGen will also deliver CRISPR with AAV because it is the most validated delivery tool clinically, Kim says. He notes that AAV is already being used in gene therapy clinical trials for Parkinsons disease, hemophilia, and vision disorders.

We are building on decades of work in gene therapy, Albright says. We believe that patients and regulators and physicians will feel more comfortable using this method. Using CRISPR in humans is enough of an unknown for Editas and ToolGen, and they believe the chances of success and drug approval are higher with an established delivery system such as AAV.

But AAVs strength for gene therapyperpetual production of a proteinis its drawback for gene editing. One of the potential issues with AAV is that there is no good way to control the expression of Cas9, says Mark Kay, director of the Program in Human Gene Therapy at Stanford University. Once inside cells, the DNA plasmid will continue producing the Cas9 enzyme indefinitely. Since CRISPR needs to make its edit only once, the longer Cas9 hangs out inside the cell, the greater the chance the enzyme will make unwanted cuts in a patients DNA, Kay says.

Those off-target cuts are frequent topics of concern among CRISPR scientists. Even though the tool is precise, there is no guarantee it will perform to perfection. That liability has driven many researchers to look for other ways of delivering CRISPR.

The challenge of commercializing CRISPR has an even closer cousin than gene therapy. Work by scientists in 1998 unexpectedly showed that double-stranded RNA molecules could suppress the translation of messenger RNA (mRNA) into protein. Known as RNA interference, or RNAi, the research garnered a Nobel Prize in 2006 and spurred the creation of start-ups aimed at turning this powerful method of silencing genes into therapies.

But RNA cannot be directly injected into the bloodstream, where it gets degraded and triggers an immune reaction. So scientists have spent the past decade figuring out how to get their molecules inside cells. Now, CRISPR researchers are hoping to borrow their most common delivery vehicle, the lipid nanoparticle.

To reuse lipid nanoparticles for CRISPR, the gene-editing system has to be packaged in a way that recapitulates the negatively charged RNA molecules used in RNAi. Instead of delivering Cas9 as a functional protein, many researchers are sticking the mRNA instructions to make Cas9 inside their nanoparticles and letting the cell produce the protein.

Andersons lab at MIT has been a center of thought for this research. Hao Yin, a postdoctoral researcher in Andersons lab, packaged Cas9 mRNA in lipid nanoparticles previously developed in the Anderson lab for shipping RNAi molecules across a cells lipid membrane. Yin then delivered that alongside guide RNAs packaged separately in AAV to fix broken genes in mice with liver disease. The upside of the method is minimal off-target cutting by Cas9. The downside is that the efficiency is very low, Yin says. Only about 6% of hepatocytes, or liver cells, were edited by CRISPR (Nat. Biotechnol. 2016, DOI: 10.1038/nbt.3471).

New and improved lipid nanoparticles are popping up that can deliver both Cas9 mRNA and the guide RNA in the same particle. Although that dual packaging would in theory improve editing efficiency, it also poses some logistical problems. The molecules used in RNAi are only about 20 nucleotides long. Guide RNAs used in CRISPR, on the other hand, are about 100 nucleotides long, and the mRNA encoding Cas9 is an unwieldy beast of 4,500 nucleotides. So if you take the off-the-shelf lipid nanoparticle formulation and instead encapsulate the CRISPR system, its just not very good, says Daniel J. Siegwart of the University of Texas Southwestern Medical Center.

Siegwart, who was previously a postdoctoral researcher in Andersons lab, became the first to successfully deliver that kind of dual packaging to mice in December. Lipid nanoparticles require several ingredients for ferrying RNA into cells, including positively charged lipids for binding the negatively charged RNA. Siegwarts group synthesized zwitterionic amino lipids, ones containing both positive and negative charges, which help bind, stabilize, and release the mRNA as the particles cross into cells (Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201610209).

Lipid nanoparticles enter cells through a pinched-off cell membrane envelope called the endosome, and getting Cas9 mRNA out of that structure can be another limiting step. In January, Paul A. Wender and Robert M. Waymouth of Stanford University unveiled a polymer nanoparticle system to overcome this problem. Their particle acts like a physical property chameleon, Wender says, changing its form as it crosses the cell membrane and enters the endosome.

Wender and Waymouths system, called charge-altering releasable transporters, are made of initially positively charged oligo(-amino ester) polymers that bind the negatively charged mRNA. Upon entering the endosome, where the pH becomes more acidic, positively charged amine molecules in the polymer become neutrally charged amides, which releases the mRNA into the cell (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1614193114). Although their paper didnt explicitly test the concept on Cas9 mRNA, thats on the to-do list.

Lipid nanoparticle innovation may be blossoming, and CRISPR developers are confident they can reach the clinic more quickly and safely than with RNAi, but that delivery vessel is by no means foolproof.

Rodger Novak, chief executive officer of CRISPR Therapeutics, whose founders include another of CRISPRs co-inventors, Emmanuelle Charpentier, points out that CRISPR has an advantage over RNAi, which turns down protein production only temporarily and needs to be readministered periodically. Those repeat injections can cause liver toxicity, a side effect that has slowed down the initially rapid progress of RNAi companies. Although the technology is maturing, there are no approved RNAi drugs.

The whole lipid nanoparticle field is a little bit weird, Ross Wilson of UC Berkeley says. The literature is full of success stories that are never followed up on; they just fizzle.

Wilson is one of several researchers working on delivering Cas9 as a protein rather than as mRNA in a lipid nanoparticle or as DNA in a virus. Researchers call this form of CRISPR a ribonucleoprotein, which is the active form of the guide RNA hooked up to the Cas9 enzyme in a single, ready-to-go complex.

David Liu of Harvard University says delivering CRISPR in a virus gives the least amount of control because it manufactures the Cas9 protein indefinitely. If there are too many Cas9 enzymes in a cell, there is a greater chance that one of them may accidentally cut DNA in the wrong place. Directly delivering the protein gives the most control because lower levels of Cas9 in each cell means a lower risk of potentially dangerous off-target cutting, Liu says. His group developed cationic lipid nanoparticles for CRISPR ribonucleoprotein delivery (Nat. Biotechnol. 2015, DOI: 10.1038/nbt.3081).

Liu, along with Qiaobing Xu of Tufts University, also created lipid nanoparticles that are biodegradable inside cells. The system binds negatively charged CRISPR ribonucleoproteins initially, but releases them upon entering the chemically reducing environment of the cell (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1520244113).

Wilson is looking to find a way to deliver CRISPR ribonucleoproteins without the hassle of lipid nanoparticles. To do that, he needs to make the ribonucleoprotein complex stable in the bloodstream, able to escape the cells endosome, and even able to home in on a particular tissue type. But there is a downside. The immunogenicity of Cas9 could be a real issue, Wilson says.

Other scientists are crafting even more exotic delivery systems for CRISPR, including a yarn ball-like structure called a DNA nanoclew developed by Chase Beisel and Zhen Gu of North Carolina State University. Their nanoclew uses repeated stretches of DNA complementary to the guide RNA wrapped up in a ball to deliver Cas9 protein to cells. (Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201506030).

Even as the field works out the delivery kinks, therapies are expected to soon reach people. Clinical trials using ex vivo gene editing in humans with CRISPR is anticipated to start in the U.S. this year, with in vivo gene editing likely in 2018 and 2019.

Casebia Therapeutics, a joint venture between Novartis and CRISPR Therapeutics, is making its commitment to the delivery challenge clear, with plans to hire a head of delivery. James Burns, CEO and president of Casebia, says, There are some approaches that we can take now, but to really harness or achieve CRISPRs full potential, we are going to have to invest in new delivery technologies. Currently, most CRISPR-based companies are taking an agnostic, whatever works approach, testing both AAV and lipid nanoparticles for their first rounds of treatment.

Berkeleys Corn points out another problem with CRISPR that many people conveniently gloss over. We are really good at breaking sequences and not really good at fixing them, he says. Some conditions can be cured using Cas9 to cut out a mutation or turn a gene off. But there are many more conditions where faulty DNA needs actual correcting. That requires a third component: a DNA template strand to tell the cells repair machinery how to fill in a cut made by Cas9.

Delivering all three has been really challenging and it has not been demonstrated in in vivo systems with any lipid nanoparticles yet, says Kunwoo Lee, who is now CEO of the start-up GenEdit that he founded in February 2016 shortly before finishing his Ph.D. in Murthys lab at Berkeley. GenEdit focuses on applications of CRISPR that will require a DNA template for repair.

Lee and his colleagues at GenEdit already have a few scientific studies under review, including one that uses gold nanoparticles as a core material to load the three components of the CRISPR system. They are also working on lipid and polymer nanoparticle systems, all designed to deliver CRISPR ribonucleoproteins. Although that strategy is promising for minimizing off-target cutting, it may also be the furthest away from being an injectable treatment in the clinic.

There is simply no way that any particular delivery modality is going to provide the means to address all of those targets, so it really needs to be an all-of-the-above approach, says Erik Sontheimer of the RNA Therapeutics Institute at the University of Massachusetts Medical School. And from the looks of it, the CRISPR companies are approaching it as such.

Ive heard many people say buckle up because there will be a trough of disillusionment that has to be traversed before it can become a clinical reality, Sontheimer says. But the potential payoff is so clear, that there will be enough staying power if and when that comes.

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CRISPR’s breakthrough problem | February 13, 2017 Issue – Vol. 95 … – The Biological SCENE

Medical schools steadily improve clinical care with research – Crain’s Detroit Business


Crain’s Detroit Business
Medical schools steadily improve clinical care with research
Crain’s Detroit Business
… study on whether intravenous delivery of nutrients into the first part of the intestine or stomach will reduce eating and improve weight-related conditions to Wayne State's novel gene therapy research for blinding eye disease, which affects 100,000

Original post:
Medical schools steadily improve clinical care with research – Crain’s Detroit Business

Vectors in gene therapy – Wikipedia

Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by several methods, summarized below. The two major classes of methods are those that use recombinant viruses (sometimes called biological nanoparticles or viral vectors) and those that use naked DNA or DNA complexes (non-viral methods).

All viruses bind to their hosts and introduce their genetic material into the host cell as part of their replication cycle. This genetic material contains basic ‘instructions’ of how to produce more copies of these viruses, hacking the body’s normal production machinery to serve the needs of the virus. The host cell will carry out these instructions and produce additional copies of the virus, leading to more and more cells becoming infected. Some types of viruses insert their genome into the host’s cytoplasm, but do not actually enter the cell. Others penetrate the cell membrane disguised as protein molecules and enter the cell.

There are two main types of virus infection: lytic and lysogenic. Shortly after inserting its DNA, viruses of the lytic cycle quickly produce more viruses, burst from the cell and infect more cells. Lysogenic viruses integrate their DNA into the DNA of the host cell and may live in the body for many years before responding to a trigger. The virus reproduces as the cell does and does not inflict bodily harm until it is triggered. The trigger releases the DNA from that of the host and employs it to create new viruses.

The genetic material in retroviruses is in the form of RNA molecules, while the genetic material of their hosts is in the form of DNA. When a retrovirus infects a host cell, it will introduce its RNA together with some enzymes, namely reverse transcriptase and integrase, into the cell. This RNA molecule from the retrovirus must produce a DNA copy from its RNA molecule before it can be integrated into the genetic material of the host cell. The process of producing a DNA copy from an RNA molecule is termed reverse transcription. It is carried out by one of the enzymes carried in the virus, called reverse transcriptase. After this DNA copy is produced and is free in the nucleus of the host cell, it must be incorporated into the genome of the host cell. That is, it must be inserted into the large DNA molecules in the cell (the chromosomes). This process is done by another enzyme carried in the virus called integrase.

Now that the genetic material of the virus has been inserted, it can be said that the host cell has been modified to contain new genes. If this host cell divides later, its descendants will all contain the new genes. Sometimes the genes of the retrovirus do not express their information immediately.

One of the problems of gene therapy using retroviruses is that the integrase enzyme can insert the genetic material of the virus into any arbitrary position in the genome of the host; it randomly inserts the genetic material into a chromosome. If genetic material happens to be inserted in the middle of one of the original genes of the host cell, this gene will be disrupted (insertional mutagenesis). If the gene happens to be one regulating cell division, uncontrolled cell division (i.e., cancer) can occur. This problem has recently begun to be addressed by utilizing zinc finger nucleases[1] or by including certain sequences such as the beta-globin locus control region to direct the site of integration to specific chromosomal sites.

Gene therapy trials using retroviral vectors to treat X-linked severe combined immunodeficiency (X-SCID) represent the most successful application of gene therapy to date. More than twenty patients have been treated in France and Britain, with a high rate of immune system reconstitution observed. Similar trials were restricted or halted in the USA when leukemia was reported in patients treated in the French X-SCID gene therapy trial.[citation needed] To date, four children in the French trial and one in the British trial have developed leukemia as a result of insertional mutagenesis by the retroviral vector. All but one of these children responded well to conventional anti-leukemia treatment. Gene therapy trials to treat SCID due to deficiency of the Adenosine Deaminase (ADA) enzyme (one form of SCID)[2] continue with relative success in the USA, Britain, Ireland, Italy and Japan.

Adenoviruses are viruses that carry their genetic material in the form of double-stranded DNA. They cause respiratory, intestinal, and eye infections in humans (especially the common cold). When these viruses infect a host cell, they introduce their DNA molecule into the host. The genetic material of the adenoviruses is not incorporated (transient) into the host cell’s genetic material. The DNA molecule is left free in the nucleus of the host cell, and the instructions in this extra DNA molecule are transcribed just like any other gene. The only difference is that these extra genes are not replicated when the cell is about to undergo cell division so the descendants of that cell will not have the extra gene. As a result, treatment with the adenovirus will require readministration in a growing cell population although the absence of integration into the host cell’s genome should prevent the type of cancer seen in the SCID trials. This vector system has been promoted for treating cancer and indeed the first gene therapy product to be licensed to treat cancer, Gendicine, is an adenovirus. Gendicine, an adenoviral p53-based gene therapy was approved by the Chinese food and drug regulators in 2003 for treatment of head and neck cancer. Advexin, a similar gene therapy approach from Introgen, was turned down by the US Food and Drug Administration (FDA) in 2008.

Concerns about the safety of adenovirus vectors were raised after the 1999 death of Jesse Gelsinger while participating in a gene therapy trial. Since then, work using adenovirus vectors has focused on genetically crippled versions of the virus.

The viral vectors described above have natural host cell populations that they infect most efficiently. Retroviruses have limited natural host cell ranges, and although adenovirus and adeno-associated virus are able to infect a relatively broader range of cells efficiently, some cell types are refractory to infection by these viruses as well. Attachment to and entry into a susceptible cell is mediated by the protein envelope on the surface of a virus. Retroviruses and adeno-associated viruses have a single protein coating their membrane, while adenoviruses are coated with both an envelope protein and fibers that extend away from the surface of the virus. The envelope proteins on each of these viruses bind to cell-surface molecules such as heparin sulfate, which localizes them upon the surface of the potential host, as well as with the specific protein receptor that either induces entry-promoting structural changes in the viral protein, or localizes the virus in endosomes wherein acidification of the lumen induces this refolding of the viral coat. In either case, entry into potential host cells requires a favorable interaction between a protein on the surface of the virus and a protein on the surface of the cell. For the purposes of gene therapy, one might either want to limit or expand the range of cells susceptible to transduction by a gene therapy vector. To this end, many vectors have been developed in which the endogenous viral envelope proteins have been replaced by either envelope proteins from other viruses, or by chimeric proteins. Such chimera would consist of those parts of the viral protein necessary for incorporation into the virion as well as sequences meant to interact with specific host cell proteins. Viruses in which the envelope proteins have been replaced as described are referred to as pseudotyped viruses. For example, the most popular retroviral vector for use in gene therapy trials has been the lentivirus Simian immunodeficiency virus coated with the envelope proteins, G-protein, from Vesicular stomatitis virus. This vector is referred to as VSV G-pseudotyped lentivirus, and infects an almost universal set of cells. This tropism is characteristic of the VSV G-protein with which this vector is coated. Many attempts have been made to limit the tropism of viral vectors to one or a few host cell populations. This advance would allow for the systemic administration of a relatively small amount of vector. The potential for off-target cell modification would be limited, and many concerns from the medical community would be alleviated. Most attempts to limit tropism have used chimeric envelope proteins bearing antibody fragments. These vectors show great promise for the development of “magic bullet” gene therapies.

A replication-competent vector called ONYX-015 is used in replicating tumor cells. It was found that in the absence of the E1B-55Kd viral protein, adenovirus caused very rapid apoptosis of infected, p53(+) cells, and this results in dramatically reduced virus progeny and no subsequent spread. Apoptosis was mainly the result of the ability of EIA to inactivate p300. In p53(-) cells, deletion of E1B 55kd has no consequence in terms of apoptosis, and viral replication is similar to that of wild-type virus, resulting in massive killing of cells.

A replication-defective vector deletes some essential genes. These deleted genes are still necessary in the body so they are replaced with either a helper virus or a DNA molecule.

[3]

Replication-defective vectors always contain a transfer construct. The transfer construct carries the gene to be transduced or transgene. The transfer construct also carries the sequences which are necessary for the general functioning of the viral genome: packaging sequence, repeats for replication and, when needed, priming of reverse transcription. These are denominated cis-acting elements, because they need to be on the same piece of DNA as the viral genome and the gene of interest. Trans-acting elements are viral elements, which can be encoded on a different DNA molecule. For example, the viral structural proteins can be expressed from a different genetic element than the viral genome.

[3]

The Herpes simplex virus is a human neurotropic virus. This is mostly examined for gene transfer in the nervous system. The wild type HSV-1 virus is able to infect neurons and evade the host immune response, but may still become reactivated and produce a lytic cycle of viral replication. Therefore, it is typical to use mutant strains of HSV-1 that are deficient in their ability to replicate. Though the latent virus is not transcriptionally apparent, it does possess neuron specific promoters that can continue to function normally[further explanation needed]. Antibodies to HSV-1 are common in humans, however complications due to herpes infection are somewhat rare.[4] Caution for rare cases of encephalitis must be taken and this provides some rationale to using HSV-2 as a viral vector as it generally has tropism for neuronal cells innervating the urogenital area of the body and could then spare the host of severe pathology in the brain.

Non-viral methods present certain advantages over viral methods, with simple large scale production and low host immunogenicity being just two. Previously, low levels of transfection and expression of the gene held non-viral methods at a disadvantage; however, recent advances in vector technology have yielded molecules and techniques with transfection efficiencies similar to those of viruses.[5]

This is the simplest method of non-viral transfection. Clinical trials carried out of intramuscular injection of a naked DNA plasmid have occurred with some success; however, the expression has been very low in comparison to other methods of transfection. In addition to trials with plasmids, there have been trials with naked PCR product, which have had similar or greater success. Cellular uptake of naked DNA is generally inefficient. Research efforts focusing on improving the efficiency of naked DNA uptake have yielded several novel methods, such as electroporation, sonoporation, and the use of a “gene gun”, which shoots DNA coated gold particles into the cell using high pressure gas.[6]

Electroporation is a method that uses short pulses of high voltage to carry DNA across the cell membrane. This shock is thought to cause temporary formation of pores in the cell membrane, allowing DNA molecules to pass through. Electroporation is generally efficient and works across a broad range of cell types. However, a high rate of cell death following electroporation has limited its use, including clinical applications.

More recently a newer method of electroporation, termed electron-avalanche transfection, has been used in gene therapy experiments. By using a high-voltage plasma discharge, DNA was efficiently delivered following very short (microsecond) pulses. Compared to electroporation, the technique resulted in greatly increased efficiency and less cellular damage.

The use of particle bombardment, or the gene gun, is another physical method of DNA transfection. In this technique, DNA is coated onto gold particles and loaded into a device which generates a force to achieve penetration of the DNA into the cells, leaving the gold behind on a “stopping” disk.

Sonoporation uses ultrasonic frequencies to deliver DNA into cells. The process of acoustic cavitation is thought to disrupt the cell membrane and allow DNA to move into cells.

In a method termed magnetofection, DNA is complexed to magnetic particles, and a magnet is placed underneath the tissue culture dish to bring DNA complexes into contact with a cell monolayer.

Hydrodynamic delivery involves rapid injection of a high volume of a solution into vasculature (such as into the inferior vena cava, bile duct, or tail vein). The solution contains molecules that are to be inserted into cells, such as DNA plasmids or siRNA, and transfer of these molecules into cells is assisted by the elevated hydrostatic pressure caused by the high volume of injected solution.[7][8][9]d

The use of synthetic oligonucleotides in gene therapy is to deactivate the genes involved in the disease process. There are several methods by which this is achieved. One strategy uses antisense specific to the target gene to disrupt the transcription of the faulty gene. Another uses small molecules of RNA called siRNA to signal the cell to cleave specific unique sequences in the mRNA transcript of the faulty gene, disrupting translation of the faulty mRNA, and therefore expression of the gene. A further strategy uses double stranded oligodeoxynucleotides as a decoy for the transcription factors that are required to activate the transcription of the target gene. The transcription factors bind to the decoys instead of the promoter of the faulty gene, which reduces the transcription of the target gene, lowering expression. Additionally, single stranded DNA oligonucleotides have been used to direct a single base change within a mutant gene. The oligonucleotide is designed to anneal with complementarity to the target gene with the exception of a central base, the target base, which serves as the template base for repair. This technique is referred to as oligonucleotide mediated gene repair, targeted gene repair, or targeted nucleotide alteration.

To improve the delivery of the new DNA into the cell, the DNA must be protected from damage and (positively charged). Initially, anionic and neutral lipids were used for the construction of lipoplexes for synthetic vectors. However, in spite of the facts that there is little toxicity associated with them, that they are compatible with body fluids and that there was a possibility of adapting them to be tissue specific; they are complicated and time consuming to produce so attention was turned to the cationic versions.

Cationic lipids, due to their positive charge, were first used to condense negatively charged DNA molecules so as to facilitate the encapsulation of DNA into liposomes. Later it was found that the use of cationic lipids significantly enhanced the stability of lipoplexes. Also as a result of their charge, cationic liposomes interact with the cell membrane, endocytosis was widely believed as the major route by which cells uptake lipoplexes. Endosomes are formed as the results of endocytosis, however, if genes can not be released into cytoplasm by breaking the membrane of endosome, they will be sent to lysosomes where all DNA will be destroyed before they could achieve their functions. It was also found that although cationic lipids themselves could condense and encapsulate DNA into liposomes, the transfection efficiency is very low due to the lack of ability in terms of endosomal escaping. However, when helper lipids (usually electroneutral lipids, such as DOPE) were added to form lipoplexes, much higher transfection efficiency was observed. Later on, it was figured out that certain lipids have the ability to destabilize endosomal membranes so as to facilitate the escape of DNA from endosome, therefore those lipids are called fusogenic lipids. Although cationic liposomes have been widely used as an alternative for gene delivery vectors, a dose dependent toxicity of cationic lipids were also observed which could limit their therapeutic usages.

The most common use of lipoplexes has been in gene transfer into cancer cells, where the supplied genes have activated tumor suppressor control genes in the cell and decrease the activity of oncogenes. Recent studies have shown lipoplexes to be useful in transfecting respiratory epithelial cells.

Polymersomes are synthetic versions of liposomes (vesicles with a lipid bilayer), made of amphiphilic block copolymers. They can encapsulate either hydrophilic or hydrophobic contents and can be used to deliver cargo such as DNA, proteins, or drugs to cells. Advantages of polymersomes over liposomes include greater stability, mechanical strength, blood circulation time, and storage capacity.[10][11][12]

Complexes of polymers with DNA are called polyplexes. Most polyplexes consist of cationic polymers and their fabrication is based on self-assembly by ionic interactions. One important difference between the methods of action of polyplexes and lipoplexes is that polyplexes cannot directly release their DNA load into the cytoplasm. As a result, co-transfection with endosome-lytic agents such as inactivated adenovirus was required to facilitate nanoparticle escape from the endocytic vesicle made during particle uptake. However, a better understanding of the mechanisms by which DNA can escape from endolysosomal pathway, i.e. proton sponge effect,[13] has triggered new polymer synthesis strategies such as incorporation of protonable residues in polymer backbone and has revitalized research on polycation-based systems.[14]

Due to their low toxicity, high loading capacity, and ease of fabrication, polycationic nanocarriers demonstrate great promise compared to their rivals such as viral vectors which show high immunogenicity and potential carcinogenicity, and lipid-based vectors which cause dose dependence toxicity. Polyethyleneimine[15] and chitosan are among the polymeric carriers that have been extensively studies for development of gene delivery therapeutics. Other polycationic carriers such as poly(beta-amino esters)[16] and polyphosphoramidate[17] are being added to the library of potential gene carriers. In addition to the variety of polymers and copolymers, the ease of controlling the size, shape, surface chemistry of these polymeric nano-carriers gives them an edge in targeting capability and taking advantage of enhanced permeability and retention effect.[18]

A dendrimer is a highly branched macromolecule with a spherical shape. The surface of the particle may be functionalized in many ways and many of the properties of the resulting construct are determined by its surface.

In particular it is possible to construct a cationic dendrimer, i.e. one with a positive surface charge. When in the presence of genetic material such as DNA or RNA, charge complimentarity leads to a temporary association of the nucleic acid with the cationic dendrimer. On reaching its destination the dendrimer-nucleic acid complex is then taken into the cell via endocytosis.

In recent years the benchmark for transfection agents has been cationic lipids. Limitations of these competing reagents have been reported to include: the lack of ability to transfect some cell types, the lack of robust active targeting capabilities, incompatibility with animal models, and toxicity. Dendrimers offer robust covalent construction and extreme control over molecule structure, and therefore size. Together these give compelling advantages compared to existing approaches.

Producing dendrimers has historically been a slow and expensive process consisting of numerous slow reactions, an obstacle that severely curtailed their commercial development. The Michigan-based company Dendritic Nanotechnologies discovered a method to produce dendrimers using kinetically driven chemistry, a process that not only reduced cost by a magnitude of three, but also cut reaction time from over a month to several days. These new “Priostar” dendrimers can be specifically constructed to carry a DNA or RNA payload that transfects cells at a high efficiency with little or no toxicity.[citation needed]

Inorganic nanoparticles, such as gold, silica, iron oxide (ex. magnetofection) and calcium phosphates have been shown to be capable of gene delivery.[19] Some of the benefits of inorganic vectors is in their storage stability, low manufacturing cost and often time, low immunogenicity, and resistance to microbial attack. Nanosized materials less than 100nm have been shown to efficiently trap the DNA or RNA and allows its escape from the endosome without degradation. Inorganics have also been shown to exhibit improved in vitro transfection for attached cell lines due to their increased density and preferential location on the base of the culture dish. Quantum dots have also been used successfully and permits the coupling of gene therapy with a stable fluorescence marker.

Cell-penetrating peptides (CPPs), also known as peptide transduction domains (PTDs), are short peptides (

CPP cargo can be directed into specific cell organelles by incorporating localization sequences into CPP sequences. For example, nuclear localization sequences are commonly used to guide CPP cargo into the nucleus.[22] For guidance into mitochondria, a mitochondrial targeting sequence can be used; this method is used in protofection (a technique that allows for foreign mitochondrial DNA to be inserted into cells’ mitochondria).[23][24]

Due to every method of gene transfer having shortcomings, there have been some hybrid methods developed that combine two or more techniques. Virosomes are one example; they combine liposomes with an inactivated HIV or influenza virus. This has been shown to have more efficient gene transfer in respiratory epithelial cells than either viral or liposomal methods alone. Other methods involve mixing other viral vectors with cationic lipids or hybridising viruses.

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Vectors in gene therapy – Wikipedia

Why bluebird bio Stock Surged 20.7% Higher in January – Motley Fool

What happened

After updating investors on its wide-ranging gene therapy research program at a key industry conference early in the month,shares ofbluebird bio(NASDAQ:BLUE) surged 20.7% higher in January,according toS&P Global Market Intelligence.

At the J.P. Morgan Healthcare Conference in early January, Bluebird Bio’s management outlined how it hopes to transform treating rare disease, including cerebral ALD (CALD), transfusion dependent beta thalassemia (TDT), and sickle cell disease.

Image source: Getty Images.

The company provided an outlook for 2022 that includes a goal of having two gene therapies on the market, two other therapies near commercialization, and four or more research programs in clinical studies.

In 2017, Bluebird Bio’s plans include prepping a filing of its TDT therapy, LentiGlobin, for approval in Europe, and developing a pathway to regulatory approval of its CALD therapy, Lenti-D.

The company is also going to continue early stage research into its CAR-T program, including its work on bb2121, a BCMA-targeting therapy that’s being developed with Celgene (NASDAQ:CELG) for multiple myeloma.

The potential to significantly reduce, or eliminate, the need for blood transfusions in TDT patients has industry watchers estimating that LentiGlobin could reshape patient treatment. If so, this gene therapy could be a nine-figure (or higher) top-seller. A similar opportunity exists for Lenti-D.

Perhaps most compelling, however, is the potential market opportunity for bb2121. Although a number of new multiple myeloma treatments have been launched over the past few years, the need for new treatment options remains high. Roughly 30,000 people are newly diagnosed with myeloma in the U.S. each year, and sadly, the five-year survival rate is just 48.5%, according to the National Cancer Institute.Clinical trials for bb2121 are early stage studies, so a lot could go wrong from here. But successfully targeting BCMA and improved outcomes without a lot of safety risks could significantly change how doctors treat their patients. If that happens, bb2121 could become a billion-dollar blockbuster someday.

Todd Campbell owns shares of Celgene.His clients may have positions in the companies mentioned.The Motley Fool owns shares of and recommends Celgene. The Motley Fool recommends Bluebird Bio. The Motley Fool has a disclosure policy.

Originally posted here:
Why bluebird bio Stock Surged 20.7% Higher in January – Motley Fool

Gene Therapy Restores Hearing Down To A Whisper, in Mice – MedicalResearch.com (blog)

MedicalResearch.com Interview with:

Dr. Gwenaelle Geleoc

Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Childrens Hospital and Harvard Medical School Boston, MA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function.

MedicalResearch.com: What should readers take away from your report? Response: This work demonstrates that gene therapy treatments can efficiently restore auditory and balance function. The level of recovery that we have obtained has never been seen before. Having identified a potent vehicle and applying the treatment at the right time was crucial in our study.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We need to extend this work to other deafness genes that lead to congenital or progressive deafness. The difficulty will arise when looking at genes that extend beyond the capacity of the vector we used for this study. Any gene over 5kb will not fit in our vector. Other strategies will therefore be required.

MedicalResearch.com: Is there anything else you would like to add? Response: Our goal is to advance research to develop new treatments for deafness and balance disorders. I welcome collaborations and material sharing with anyone who wish to work with us for this purpose.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Gwenalle S Gloc et al. Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. Nature Biotechnology, February 2017 DOI: 10.1038/nbt.3801

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Gene Therapy Restores Hearing Down To A Whisper, in Mice – MedicalResearch.com (blog)

Why bluebird bio Stock Surged 20.7% Higher in January – Fox Business

What happened

After updating investors on its wide-ranging gene therapy research program at a key industry conference early in the month,shares ofbluebird bio(NASDAQ: BLUE) surged 20.7% higher in January,according toS&P Global Market Intelligence.

At the J.P. Morgan Healthcare Conference in early January, Bluebird Bio’s management outlined how it hopes to transform treating rare disease, including cerebral ALD (CALD), transfusion dependent beta thalassemia (TDT), and sickle cell disease.

Image source: Getty Images.

The company provided an outlook for 2022 that includes a goal of having two gene therapies on the market, two other therapies near commercialization, and four or more research programs in clinical studies.

Continue Reading Below

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In 2017, Bluebird Bio’s plans include prepping a filing of its TDT therapy, LentiGlobin, for approval in Europe, and developing a pathway to regulatory approval of its CALD therapy, Lenti-D.

The company is also going to continue early stage research into its CAR-T program, including its work on bb2121, a BCMA-targeting therapy that’s being developed with Celgene (NASDAQ: CELG) for multiple myeloma.

The potential to significantly reduce, or eliminate, the need for blood transfusions in TDT patients has industry watchers estimating that LentiGlobin could reshape patient treatment. If so, this gene therapy could be a nine-figure (or higher) top-seller. A similar opportunity exists for Lenti-D.

Perhaps most compelling, however, is the potential market opportunity for bb2121. Although a number of new multiple myeloma treatments have been launched over the past few years, the need for new treatment options remains high. Roughly 30,000 people are newly diagnosed with myeloma in the U.S. each year, and sadly, the five-year survival rate is just 48.5%, according to the National Cancer Institute.Clinical trials for bb2121 are early stage studies, so a lot could go wrong from here. But successfully targeting BCMA and improved outcomes without a lot of safety risks could significantly change how doctors treat their patients. If that happens, bb2121 could become a billion-dollar blockbuster someday.

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Todd Campbell owns shares of Celgene.His clients may have positions in the companies mentioned.The Motley Fool owns shares of and recommends Celgene. The Motley Fool recommends Bluebird Bio. The Motley Fool has a disclosure policy.

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Why bluebird bio Stock Surged 20.7% Higher in January – Fox Business

Stanford scientists describe stem-cell and gene-therapy advances in scientific symposium – Scope (blog)

Using stem cells and gene therapy to treat orcure disease may still sound like science fiction, but a scientific meeting here last week emphasizedall the fronts onwhich it is moving closer and closer to fact.

Were entering a new era in medicine, said Lloyd Minor, MD, dean of the School of Medicine, in his opening remarks at the first annual symposium of the schools new Center for Definitive and Curative Medicine. Stanford researchersare poised to use stem cells and gene therapy to amelioratea wide swath of diseases, from common diagnoses such as diabetes and cancerto rare diseases ofthe brain, blood, skin, immune system and other organs. Ultimately, the goal is to create one-time treatments that can provide lifetime cures; hence the definitive and curative part of the centers name. Stanford is a leader in this branch of medical research, Minor said, addingThis is a vital component of our vision for precision health.

Stanford has a long history of leading basic-science discoveries in stem cell biology, andis now engaged in studyingmany different ways those discoveries couldbenefit patients, saidMaria Grazia Roncarolo, MD, who leads the new center.Our job is to produce clinical data so compelling that industry will pick up the product and take it to the next stage, Roncaraolo told the audience.

Among otherevent highlights:

More coverage of the days events is available in a story from the San Jose Mercury News that describeshowAnthonyOro, MD, PhD, and his colleagues are fighting epidermolysis bullosa, a devastating genetic disease of the skin. Oro closed his talk with a slightly goofy photo of a man getting a spray tan. It got a laugh, but his point was serious: Our goal for the cell therapy of the future is spray-on skin to correct a horrible genetic disease.

Ambitious? Yes. Science fiction? In the future, maybe not.

Previously: One of the most promising minds of his generation: Joseph Wu takes stem cells to heart,Life with epidermolysis bullosa: Pain is my reality, pain is my normaland Rat-grown mouse pancreases reverse diabetes in mice, say researchers Photo of Matthew Porteus courtesy of Stanford Childrens

Link:
Stanford scientists describe stem-cell and gene-therapy advances in scientific symposium – Scope (blog)

Gene Therapy to Restore Hearing | Worldhealth.net Anti-Aging News – Anti Aging News

Posted on Feb. 8, 2017, 6 a.m. in Gene Therapy Sensory

Harvard Medical School scientists have perfected a form of gene therapy that has enabled genetically deaf mice to hear sounds as quiet as a whisper.

Harvard Medical School scientists have perfected gene therapy to the point that it can restore hearing. Their research and experiments have shown that the hearing of genetically deaf mice can be restored to the point that they hear noises at 25 decibels. This decibel level is equivalent to that of a soft whisper.

The Nuances of Gene Therapy for Improved Hearing

Harvard’s gene therapy researchers state the most important aspect of their gene therapy breakthrough is a vector they created known as “Anc80”. This vector brings a therapeutic gene to the cells within the cochlea’s outer ear that are quite difficult to access. These outer hair cells boost sound, empowering inner hair cells to transmit a much more powerful communication to the brain. Gwenalle Gloc of Boston Children’s Hospital’s Department of Otolaryngology and F.M. Kirby Neurobiology Center, states the new system functions quite well by rescuing vestibular and auditory function to a degree that was not previously achieved in medical history. Research Details

Harvard’s research team includes scientists employed by Massachusetts Eye and Ear. The group tested its gene therapy technique on mice with Usher Syndrome. This is a genetic disease that harms hearing as well as vision. Humans who are saddled with this disease are afflicted with a gene mutation that makes the protein harmonin ineffective. As a result, the hair cells responsible for accepting auditory signals and transmitting them to the brain are rendered useless.

The research team tapped into the power of its new vector to transmit an improved version of the gene, referred to as Ush1c, directly into the ear. It didn’t take long for the ear’s outer and inner hair cells to generate effective harmonin. Subsequent hearing tests conducted on mice proved that animals born deaf could hear. Some of these mice could even pick up on uber-soft auditory signals just like their normal peers.

The Magic of Gene Therapy

The scientific community is abuzz over gene therapy. Some believe gene therapy will ultimately prove to be the cure for deafness. It was only two years ago when scientists and investigators from Harvard and the University of Michigan’s Hearing Research Institute found that the hearing-associated protein, NT3, can be stimulated through gene therapy. Additional approaches are geared toward stimulating the regeneration of hair cells within the ear. As an example, Harvard researchers have found that drugs referred to as Notch inhibitors can spur existing ear cells to transition into hair cells that improve hearing in mice.

The Harvard team reports its latest success with gene therapy made use of a similar technique that heightened hearing in 2015. However, these researchers now believe their newly generated vector will restore an even higher level of auditory ability. They also noted that the Ush1c gene applied to deaf mice served to heighten their balance. Mice with Usher Syndrome typically suffer from such poor balance. The Future of Gene Therapy

The future looks quite bright for those who suffer from hearing deficiencies. The research described above is fantastic news for those who suffer from hearing loss. It is possible that gene therapy will eventually supplant cochlear implants that are currently used to improve hearing in young patients. Though Cochlear implants have served patients quite well, there is still room for improvement.

Patients would like to hear an extended range of frequencies and the direction of a sound’s source. They would also like to be able to differentiate between the auditory nuances of background noise, voices, music etc. The added benefit of heightened physical balance will serve to enhance Usher Syndrome patients’ balance and mobility.

More:
Gene Therapy to Restore Hearing | Worldhealth.net Anti-Aging News – Anti Aging News

Gene Therapy for Heart Disease Wins Fast-Track Status | P&T … – P&T Community

Gene Therapy for Heart Disease Wins Fast-Track Status | P&T …
P&T Community
The FDA has granted a fast-track designation for a phase 3 study of Generx (Ad5FGF-4, Angionetics Inc.) cardiovascular angiogenic gene therapy as a one-time …

and more »

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Gene Therapy for Heart Disease Wins Fast-Track Status | P&T … – P&T Community

Gene therapy’s latest benefit: New skin – Daily Democrat

Small sheets of healthy skin are being grown from scratch at a Stanford University lab, proof that gene therapy can help heal a rare disease that causes great human suffering.

The precious skin represents growing hope for patients who suffer from the incurable blistering disease epidermolysis bullosa and acceleration of the once-beleaguered field of gene therapy, which strives to cure disease by inserting missing genes into sick cells.

It is pink and healthy. Its tougher. It doesnt blister, said patient and research volunteer Monique Roeder, 33, of Cedar City, Utah, who has received grafts of corrected skin cells, each about the size of an iPhone 5, to cover wounds on her arms.

More than 10,000 human diseases are caused by a single gene defect, and epidermolysis bullosa is among the most devastating. Patients lack a critical protein that binds the layers of skin together. Without this protein, the skin tears apart, causing severe pain, infection, disfigurement and in many cases, early death from an aggressive form of skin cancer.

The corrected skin is part of a pipeline of potential gene therapies at Stanfords new Center for Definitive and Curative Medicine, announced last week.

The center, a new joint initiative of Stanford Healthcare, Stanford Childrens Health and the Stanford School of Medicine, is designed to accelerate cellular therapies at the universitys state-of-the-art manufacturing facility on Palo Altos California Avenue. Simultaneously, it is aiming to bring cures to patients faster than before and boost the financial value of Stanfords discoveries before theyre licensed out to biotech companies.

With trials such as these, we are entering a new era in medicine, said Dr. Lloyd B. Minor, dean of the Stanford University School of Medicine.

Gene therapy was dealt a major setback in 1999 when Jesse Gelsinger, an Arizona teenager with a genetic liver disease, had a fatal reaction to the virus that scientists had used to insert a corrective gene.

But current trials are safer, more precise and build on better basic understanding. Stanford is also using gene therapy to target other diseases, such as sickle cell anemia and beta thalassemia, a blood disorder that reduces the production of hemoglobin.

There are several diseases that are miserable and worthy of gene therapy approaches, said associate professor of dermatology Dr. Jean Tang, who co-led the trial with Dr. Peter Marinkovich. But epidermolysis bullosa, she said, is one of the worst of the worst.

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It took nearly 20 years for Stanford researchers to bring this gene therapy to Roeder and her fellow patients.

It is very satisfying to be able to finally give patients something that can help them, said Marinkovich. In some cases, wounds that had not healed for five years were successfully healed with the gene therapy.

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Gene therapy’s latest benefit: New skin – Daily Democrat

Gene therapy: Deaf to hearing a whisper – BBC News


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Gene therapy: Deaf to hearing a whisper – BBC News

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