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Archive for the ‘Gene Therapy Research’ Category

What is Gene Therapy? | Pfizer: One of the world’s premier …

Gene therapy is a technology aimed at correcting or fixing a gene that may be defective. This exciting and potentially transformative area of research is focused on the development of potential treatments for monogenic diseases, or diseases that are caused by a defect in one gene.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

Viral vectors can be developed using adeno-associated virus (AAV), a naturally occurring virus which has been adapted for gene therapy use. Its ability to deliver genetic material to a wide range of tissues makes AAV vectors useful for transferring therapeutic genes into target cells. Gene therapy research holds tremendous promise in leading to the possible development of highly-specialized, potentially one-time delivery treatments for patients suffering from rare, monogenic diseases.

Pfizer aims to build an industry-leading gene therapy platform with a strategy focused on establishing a transformational portfolio through in-house capabilities, and enhancing those capabilities through strategic collaborations, as well as potential licensing and M&A activities.

We're working to access the most effective vector designs available to build a robust clinical stage portfolio, and employing a scalable manufacturing approach, proprietary cell lines and sophisticated analytics to support clinical development.

In addition, we're collaborating with some of the foremost experts in this field, through collaborations with Spark Therapeutics, Inc., on a potentially transformative gene therapy treatment for hemophilia B, which received Breakthrough Therapy designation from the US Food and Drug Administration, and 4D Molecular Therapeutics to discover and develop targeted next-generation AAV vectors for cardiac disease.

Gene therapy holds the promise of bringing true disease modification for patients suffering from devastating diseases, a promise were working to seeing become a reality in the years to come.

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What is Gene Therapy? | Pfizer: One of the world's premier ...

STAR Gene Therapy | Charcot-Marie-Tooth Association

The CMTA Is Accelerating Research Through Gene Therapy

The CMTA looks forward to a time when doctors are able to use genetic therapies to treat the root cause of CMT rather than prescribing medications or recommending surgery. We are already envisioning the possibilities that gene therapy holds for our community of 2.8 million people worldwide living with CMT. In fact, were leading the pursuit to explore gene therapy in CMT by expanding our Strategy to Accelerate Research (STAR) program and our STAR Advisory Board.

At the CMTA, we are already envisioning the possibilities that gene therapy holds for our community of 2.8 million people worldwide living with CMT. John Svaren, PhD, Chair, CMTA Scientific Advisory Board

Given the increased feasibility and applicability of gene therapy to CMT, the CMTA hosted a Gene Therapy Workshop in 2018. In response to invitations from CMTA board member Dr. Steven Scherer, more than 20 of the top gene therapy experts gathered for the inaugural CMT-centered workshop on gene therapy. This meeting included experts who have worked in related genetic and neuromuscular disease areas, as well as clinicians and scientists spearheading efforts toward gene therapy for CMT2D and CMT4J.

Building on this meeting, the CMTA is assembling the best experts to formulate gene therapy strategies for CMT2 and CMT1 subtypes. Four gene therapy experts, Beverly Davidson, PhD, at the University of Pennsylvania, Kleopas Kleopa, MD, at the Cyprus Institute of Neurology & Genetics, Scott Harper, PhD, at the Ohio State University School of Medicine, and Steven Gray, PhD, at the University of Texas Southwestern Medical Center have now joined the Scientific Advisory Board of the CMTA. Dr. Davidson is an acknowledged leader in the gene therapy field, and her extensive experience includes both academic research and commercial translation gene therapy approaches. Dr. Kleopa has shown proof of concept that gene therapy works in two mouse models of CMT: CMT1X and CMT4C. This strategy can capitalize on the CMT animal models that have been developed and characterized with CMTA support. Dr. Harper is collaborating with Robert Burgess, PhD, at the Jackson Laboratory to develop a gene therapy vector to be used in a treatment for CMT2D. Dr. Grays core expertise is in Adeno-Associated Virus (AAV) gene therapy vector engineering, followed by optimizing approaches to deliver a gene to the nervous system, with application to CMT4J.

Our genes dictate many of our personal characteristics; however, mutations in genes cause genetic diseases, such as CMT. Scientists have been working for decades to modify or replace faulty genes with healthy ones to treat, cure or prevent disease. Fortunately, we are seeing significant progress on these efforts to provide gene therapy options for CMT. In fact, recent studies have provided an effective gene therapy for spinal muscular atrophy (SMA), a devastating disorder that affects the same motor neurons that are affected by CMT.

Sometimes the whole gene is duplicated, as in CMT1A, where a chromosome segment around the PMP22 gene is present in three copies instead of two. Alternatively, a part of a gene is defective or missing from birth, causing many of the other known forms of CMT. Any of these variations can disrupt the structure of the protein that is encoded by the affected gene, causing cellular problems that ultimately lead to disease.

In gene therapy, scientists can do one of several things depending on the problem with the gene. The simplest form of gene therapy is to simply provide a correct copy of the gene, which is the basis of the gene therapy for SMA. In variations of this approach, genes that are causing problems can be suppressed. One example of this was the recent demonstration that antisense oligonucleotides can be used to improve the neuropathy in rodent models of CMT1A. In addition, the exciting new field of genome editing using CRISPR technology has now made it possible to correct disease-causing mutations, and collaborative projects have already been initiated with leaders in this field

In order to insert new genes directly into cells, scientists use a vehicle called a vector that is genetically engineered to deliver the correct version of the gene. For example, viruses have a natural ability to deliver genetic material into cells, and therefore, can be used as vectors. While some viruses cause disease, virus vectors are highly modified to remove their ability to cause disease so that they can be safely used to carry therapeutic genes into human cells.

Gene therapy can be used to modify cells inside or outside the body. When its done inside the body, a doctor will inject the vector carrying the gene directly into the part of the body that has defective cells.

Before a company can market a gene therapy product for use in humans, the gene therapy product has to be tested for safety and effectiveness so that the Food and Drug Administration (FDA) can evaluate whether the risks of the therapy are acceptable in light of its potential benefits. Gene therapies have begun to receive FDA approval, and many gene therapies are in clinical trials.

At the CMTA, we believe gene therapy holds the promise to provide effective therapies for people living with CMT. As we continue to make great strides in this area, the CMTA is committed to helping speed the development of gene therapy approaches by investing in the most promising and groundbreaking gene therapy treatments that have the potential to benefit our community.

We are members of the National Organization for Rare Disorders (NORD), and they have put together a six-minute video to help answer questions frequently asked about gene therapy. We think this video will help you better understand the basics of gene therapy.

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STAR Gene Therapy | Charcot-Marie-Tooth Association

Gene Therapy to Treat Macular Degeneration – AMDF

In Boston, scientists are working at the frontier of genetic research in an attempt to cure Macular Degeneration, the leading cause of blindness in the U.S., an enormous task.

Rajendra Kumar-Singh: There are about 3 billion nucleotides in the human genome and just 1 small mistake is sufficient to cause a problem. And when that problem occurs it can lead to inherited retinal degeneration.

Dean Bok: The promises of gene therapy at this point in time are tremendous. In principal, one can replace a bad gene with a good one. Its easier to replace a gene thats recessive, where you need two bad ones in order to produce the disease, and thats where weve had success. The challenge is for genes that are dominant. You need to get rid of the bad guys before the good guys can do their work.

Rajendra Kumar-Singh: Because the source of inherited retinal degeneration is DNA, it makes sense to be able to deliver normal DNA to correct the defect and hence gene therapy is going to be a key player in trying to develop novel therapies for these inherited retinal degeneration.

Narrator: (Animation) An imbalance in the complement system, which helps to fight many diseases, can cause holes or, macs, to form in the macula. A protein called cd59 normally helps prevent this from occurring. At Tufts University they are seeking a way to increase this protein in people with macular degeneration.

Rajendra Kumar-Singh: We plan to express the same protein but at higher levels on the cells that are normally getting damaged in AMD and theoretically we hope to be able to prevent the formation of these macs on these cells. When we use gene therapy we are in fact putting back in a normal version of the gene, such as the protein that is produced from that is now normal and allows the cell to revert to a normal, healthy looking or healthy functioning cell. We can potentially inject just once directly into the eye and that may serve as a therapeutic for the lifetime of the patient whether it be dry AMD or wet AMD. Science is all about solving problems and I would love to be the one to be able to solve this problem and provide some sort of therapies to people who otherwise might potentially go blind. And I think Ill have fulfilled my role as a scientist if I can achieve that.

Rajendra Kumar-Singh, PhD, Professor of Ophthalmology and NeuroscienceTufts University

Dean Bok, Phd, Distinguished Professor of Neurobiology and OphthalmologyUCLA

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Gene Therapy to Treat Macular Degeneration - AMDF

Amicus Establishes Global Research and Gene Therapy Center …

New 75,000 sq. ft. State of the Art Facility in uCity Square Adjacent to Penn Campus

Strengthens Amicus Capabilities as a Leading Global Rare Disease Biotechnology Company

CRANBURY, N.J. and PHILADELPHIA, Feb. 26, 2019 (GLOBE NEWSWIRE) -- Amicus Therapeutics (FOLD) today announced it is establishing a new Global Research and Gene Therapy Center of Excellence in uCity Square in Philadelphia, PA, to advance its commitment to world-class science that makes a meaningful difference in the lives of people living with rare metabolic diseases. Philadelphia is a well-regarded ecosystem for biotechnology and gene therapy research and offers an ideal environment for Amicus to advance its pipeline, attract and retain top talent and foster external collaborations within the rare diseases.

John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, stated, This Amicus Global Research and Gene Therapy Center of Excellence is an important next step in the evolution of our science, research and gene therapy capabilities. In considering locations, Philadelphia became the clear choice as a burgeoning hub for medical breakthroughs. The proximity to our collaborators at the University of Pennsylvania and other major academic centers and hospitals in the area also provides a tremendous opportunity to advance our commitment to gene therapies. Philadelphia is easily accessible to New Jersey, which has been a strong contributor to our success and will remain the location of our global headquarters. As Amicus continues to expand globally, my hope is that the great science to come from our research in Philadelphia will one day soon lead to medicines with the potential to alleviate an enormous amount of suffering. This is our mission at Amicus and we are honored to be a part of the exciting Philadelphia research community.

Under the leadership of Jeff Castelli, PhD, Chief Portfolio Officer and newly appointed Head of Gene Therapy, and Hung Do, PhD, Chief Science Officer, the new facility will be located at 3675 Market Street in uCity Square, a 6.5 million square-foot, mixed-use knowledge community consisting of office, laboratory, clinical, residential and retail space designed to enable university and corporate research, entrepreneurial activity and community engagement.

An initial group of Amicus research employees has moved into temporary space in the building at BioLabs@CIC Philadelphia during construction of the permanent space. The new 75,000 sq. ft. Center will be completed in the second half of 2019 and will serve as the headquarters for the global Amicus science organization and the gene therapy leadership team. Amicus expects up to 200 employees to eventually be based at the new Philadelphia facility. The Company is maintaining global business operations in Cranbury, NJ, and international headquarters in Marlow, UK.

J. Larry Jameson, MD, PhD, Executive Vice President for the Health System and Dean of the Raymond and Ruth Perelman School of Medicine stated, On behalf of Penn Medicine, I would like to welcome Amicus Therapeutics to Philadelphia. Amicus is working to pioneer significant advancements in gene therapy, which includes a collaboration with Dr. James Wilson and his team at our Orphan Disease Center. This relationship reflects how the innovation ecosystem at Penn brings together researchers, innovators, and entrepreneurs to accelerate research discoveries to patients as quickly as possible. The close proximity between the Amicus Center of Excellence and our campus will further strengthen this relationship and create additional opportunities to work together.

Jim Kenney, Mayor of Philadelphia, commented, The City of Philadelphia is committed to fostering innovative companies, academic institutions, and hospitals that are focused on the latest advancements in research and development, while also elevating the patient experience within our healthcare systems. Amicus Therapeutics is an established leader in biotechnology with a unique and intense patient-dedicated mission. The Companys presence and investment in Philadelphia will create additional opportunities that will be highly influential as our city continues its transformation into a major global biotech hub.

About Amicus Therapeutics Amicus Therapeutics (FOLD) is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare metabolic diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a robust pipeline of cutting-edge, first- or best-in-class medicines for rare metabolic diseases. For more information please visit the companys website at http://www.amicusrx.com, and follow us on Twitter and LinkedIn.

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Forward-Looking StatementsThis press release contains "forward- looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 Words such as, but not limited to, look forward to, believe, expect, anticipate, estimate, intend, "confidence," "encouraged," potential, plan, targets, likely, may, will, would, should and could, and similar expressions or words identify forward-looking statements. The forward looking statements included in this press release are based on management's current expectations and belief's which are subject to a number of risks, uncertainties and factors. In addition, all forward looking statements are subject to the other risks and uncertainties detailed in our Annual Report on Form 10-K for the year ended December 31, 2017 and Quarterly Report on 10-Q for the Quarter ended September 30, 2018. As a consequence, actual results may differ materially from those set forth in this press release. You are cautioned not to place undue reliance on these forward looking statements, which speak only of the date hereof. All forward looking statements are qualified in their entirety by this cautionary statement and we undertake no obligation to revise this press release to reflect events or circumstances after the date hereof.

CONTACTS:

Investors/Media:Amicus TherapeuticsSara Pellegrino, IRCVice President, Investor Relations & Corporate Communicationsspellegrino@amicusrx.com (609) 662-5044

Media:Amicus TherapeuticsMarco WinklerDirector, Corporate Communicationsmwinkler@amicusrx.com(609) 662-2798

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Amicus Establishes Global Research and Gene Therapy Center ...

Journal of Stem Cell Research and Therapy- Open Access …

PUBMED NLM ID: 101586297 | Index Copernicus Value: 84.95 The Journal of Stem Cell Research & Therapy is an open access journal that showcases seminal research in the field of stem cell therapy. As stem-cells are flag-bearers of translational research, the field has an interdisciplinary feel by including oncology, clinical research, medicine and healthcare under the aegis of stem-cell therapy. It also includes scientific research related to the auxiliary areas of Biology by prioritizing scholarly communication milieu and transfers expert knowledge synthesized from the ever burgeoning stem-cell literature. In order to create such impactful content, the Journal of Stem Cell Research & Therapy brings together an expert Editorial Board, which comprises of noted scholars in the field of Cell Biology. Every single article is subjected to rigorous peer review by illustrious scientists. In addition to Research Articles, the Journal also publishes high quality Commentaries, Reviews, and Perspectives aimed at synthesizing the latest developments in the field, and putting forward new theories in order to provoke debates amongst the scholars in the field. The journal thus maintains the highest standards in terms of quality and comprehensive in its approach.The journal aims to provide the authors with an efficient and courteous editorial platform. The authors can be assured of an expeditious publishing process. In this regard, the journal also provides advance online posting of the accepted articles. The Journal of Stem Cell Research & Therapy ensures barrier-free, open access distribution of its content online and thus, helps in improving the citations for authors and attaining a good impact factor.

Scholarly Journal of Stem Cell Research & Therapy is using online manuscript submission, review and tracking systems of Editorial Manager for quality and quick review processing. Review processing is performed by the editorial board members of Journal of Stem Cell Research and Therapy or outside experts; at least two independent reviewers approval followed by editor approval is required for acceptance of any citable manuscript.

It is an undifferentiated cell which is capable of transforming into more cells of same type or multiple other types. They are found in multicellular organisms. They can differentiate into cells of blood, skin, heart, muscles, brain etc. In adult human being, they replenish the dead cells of various organs. Stem cells are being used for treatment of various diseases like diabetes, arthritis, few cancers, bone marrow failure etc.

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They can develop into any cell type or organ in the body. A single totipotent stem cell can give rise to an entire organism. Fertilized egg or a zygote is the best example. Zygote divides and produces more totipotent cells. After 4 days the cells lose totipotency and become pluripotent.

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They can differentiate into any cell type in the human body. Embryonic stem cells are mostly pluripotent stem cells. They have the ability to differentiate into any of three germ layers: endoderm, mesoderm, or ectoderm.

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These are multipotent stem cells normally found in the bone marrow and are derived from mesenchyme. They differentiate into adipocytes, chondrocytes, osteoblasts, myocytes and tendon. MSCs can also be extracted from blood, fallopian tube, fetal liver and lungs.

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They are the multipotent stem cells derived from mesoderm and located in red bone marrow. They are responsible for production of red blood cells, white blood cells and platelets. HSCs give rise to myeloid lineage (which forms erythrocytes, eosinophils, basophils, neutrophils, macrophages, mast cells and platelets) and lymphoid lineage (which forms T-lymphocytes, plasma cells and NK cells).

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They can differentiate into more than one cell type, but only into a limited number of cell types. Hematopoietic stem cells are considered multipotent as they can differentite into red blood cells, platelets, white blood cells but they cannot differentiate into hepatocytes or brain cells.

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Cells with stem cell like abilities have been observed breast cancer, colon cancer, leukemia, melanoma, prostate cancer which can form new cells and lead to tumorigenesis. They cause relapse and metastasis by giving rise to new tumors. Scientists are developing methods to destroy CSCs in place of traditional methods which focus on bulk of cancer cells.

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They are derived from Hematopoietic stem cells. They differentiate into Erythrocyte progenitor cell (forms erythrocytes), Thrombocyte progenitor cell (forms platelets) and Granulocyte-Monocyte progenitor cell (forms monocytes, macrophages, neutrophils, basophils, eosinophils, dendritic cells).

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They are the self-renewing, multipotent stem cells in the nervous system that differentiate into neurons, astrocytes and oligodendrocytes. They repair the nervous system after damage or an injury. They have potential clinical use the management of Parkinsons disease, Huntingtons disease and multiple sclerosis.

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They are derived from embryo in the blastocyst stage. They are pluripotent stem cells. They give rise to all derivatives of the three primary germ layers: endoderm (stomach, colon, liver, pancreas, intestines etc.), mesoderm (muscle, bone, cartilage, connective tissue, lymphatic system, circulatory system, genitourinary system etc.) and ectoderm (brain, spinal cord, epidermis etc.).

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Embryonic stem cells are derived from the fetus are used in treatment of various diseases. As ESCs are pluripotent, they can differentiate into any cell type. Researchers are able to grow ESCs into complex cells types like pancreatic -cells and cardiocytes. Fetal cell therapy is generating lot of controversy from religious groups and ethics committees.

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Research is being done to use stem cells for the treatment of diabetes mellitus. Human embryonic stem cells may be grown in vivo and stimulated to produce pancreatic -cells and later transplanted to the patient. Its success depends on response of the patients immune system and ability of the transplanted cells to proliferate, differentiate and integrate with the target tissue.

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The procedure to replace damaged cells (in cancers, aplastic anemia etc.) with healthy stem cells of the same person or in another compatible person to restore the normal production of cells. It can either be autologous or allogeneic. Bone marrow HSCs are generally used for the transplantation.

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They are the totipotent, undifferentiated cells present in the meristems (shoot and root apices) of a plant. They never undergo aging process and can grow into any cell in the plant throughout its lifetime. They have numerous applications in production of cosmetics, perfumes, pigments, insecticides and antimicrobials.

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Several types of dental stem cells have been isolated from mature and immature teeth, exfoliated deciduous teeth and apical papilla, MSCS from tooth germs and from human periodontal ligament. They are found to be multipotent and can give rise to osteogenic, adipogenic, myogenic and neurogenic cell lineages.

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Adipose tissue is a huge source of mesenchymal stem cells which differentiate into various cell types. They can be easily extracted in large numbers by a simple lipo-aspiration. They have good application potential in regenerative medicine. ASCs are found to have the ability to differentiate into bone cells, cartilage cells, nerve cells, adipocytes etc.

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Preservation of stem cells is critical for both research and clinical application of stem-cell based therapies. Properly preserved stem cells can be later used in the field of regenerative medicine for treating congenital disorders, heart defects etc. Currently there is no universal method for preserving stem cells and the existing methods are expensive.

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MSCs can be applied in osteoarthritis treatment through implantation and microfracture as well as intra-articular injections. Single injection studies have showed improvement from pain which decreased overtime. Multiple, regular MSC injections into joints may be necessary.

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OMICS International through its Open Access Initiative is committed to make genuine and reliable contributions to the scientific community. OMICS International hosts over 700 leading-edge peer reviewed Open Access Journals and organizes over 1000 International Conferences annually all over the world. OMICS International journals have over 10 million readers and the fame and success of the same can be attributed to the strong editorial board which contains over 50000 eminent personalities that ensure a rapid, quality and quick review process. OMICS International signed an agreement with more than 1000 International Societies to make healthcare information Open Access. OMICS International Conferences make the perfect platform for global networking as it brings together renowned speakers and scientists across the globe to a most exciting and memorable scientific event filled with much enlightening interactive sessions, world class exhibitions and poster presentations.

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Journal of Stem Cell Research and Therapy- Open Access ...

Gene Therapy Initiative – gilbertfamilyfoundation.org

Exploring Nonsense Suppressionas a Treatment for NF1

This project aims to find compounds that suppress the effects of nonsense mutations in the NF1 gene, thus restoring neurofibromin protein expression and function in NF1 patients.

David Bedwell, PhDUniversity of Alabama, Birmingham

Bruce Korf, MD, PhDUniversity of Alabama, Brimingham

Mark Suto, PhDSouthern Research

This project will resolve two primary challenges applying gene therapy approaches to NF1 by using an innovative strategy to engineer new viruses that targets tumor initiating cells and CRISPR-based genome editing to restore the mutated NF1 gene. Using a unique team with complimentary expertise, this venture applies some of the most exciting modern biotechnologies to NF1.

Charles Gersbach, PhDDuke University

David V. Schaffer, PhDUniversity of California, Berkeley

David G. Kirsch, MD, PhDDuke University

Ataluren is a drug that can suppress protein synthesis termination at premature nonsense codons to produce essential proteins in patients with Duchenne muscular dystrophy. This project aims to evaluate its effect on mouse cells with an NF1 gene that harbors nonsense mutations.

Allan Jacobson, PhDUniversity of Massachusetts

This project proposes using nanoparticles to deliver 1) key coding regions of NF1 gene (cDNA) that will make neurofibromin protein, and 2) gene-editing regents to directly correct the mutation that causes NF1 in a patient derived NF1 rat model. If successful, the new system will provide essential pre-clinical data and lay the foundation for clinical trials using nanomedicine to treat NF1 disease.

Robert Kesterson, PhDUniversity of Alabama, Birmingham

Jiangbing Zhou, PhDYale University

This project will bioengineer trans-acting ribozymes, RNA molecules with catalytic properties similar to protein enzymes, to target faulty transcripts of the NF1 gene that fail to translate functional neurofibromin. NF1 mouse models with patient specific mutations that are amenable to ribozyme-mediated correction will be developed for subsequent animal studies.

Andr Leier, PhD University of Alabama, Birmingham

Ulrich Muller, PhDUniversity of California, San Diego

The mutation of one gene, e.g. NF1, often makes other genes that are not normally required for cell survival vulnerable to inactivation. This project aims to kill cells that have inactivated both copies of the NF1 gene. Using CRISPR/CAS9 technology, genes that become essential for the survival of cells with inactivated both copies of the NF1 gene will be identified, particularly those for which an FDA-approved drug is already available.

Eric Pasmant, PharmD, PhDUniversity Paris Descartes

Raphal Margueron, PhDInstitut Curie

This project seeks to develop two new NF1 drug candidates by developing and characterizing multiple potential therapeutics in parallel within fourteen research laboratories. AAV vectors for delivery and zinc finger protein and antisense oligonucleotides to upregulate NF1 expression will also be used when evaluating the efficacy of different therapeutic modalities.

Miguel Sena-Esteves, PhDUniversity of Massachusetts

Scot Wolfe, PhDUniversity of Massachusetts

Matthew Gounis, PhDUniversity of Massachusetts

Jonathan Watts, PhDUniversity of Massachusetts

Xandra Breakefield, PhDMassachusetts General Hospital

Casey Maguire, PhDMassachusetts General Hospital

Antisense directed gene therapy, or more specifically exon skipping, causes cells to skip over faulty pieces of the genetic code, leading to a truncated, but still functional, protein. This project aims to identify exons within the NF1 gene that may be skipped while still maintaining gene function and then develop antisense oligonucleotides to enable modulation of expression.

Deeann Wallis, PhDUniversity of Alabama, Birmingham

Linda Popplewell, PhDRoyal Holloway University of London

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Gene Therapy Initiative - gilbertfamilyfoundation.org

AveXis Research & Development

The U.S. Food and Drug Administration (FDA) has granted AVXS-101 Orphan Drug Designation for the treatment of all types of SMA and Breakthrough Therapy Designation, as well as Fast Track Designation, for the treatment of SMA Type 1.

The European Medicines Agency (EMA) also granted AveXis access into its PRIority Medicines (PRIME) program for AVXS-101 for the treatment of SMA Type 1.

The open-label, single-arm, single-dose, multi-center trial known as STR1VE is designed to evaluate the efficacy and safety of a one-time IV infusion of AVXS-101 in patients with SMA Type 1. The co-primary efficacy outcome measures of the trial include the achievement of independent sitting for at least 30 seconds at 18 months of age; and, event-free survival at 14 months of age. Co-secondary outcome measures include the ability to thrive, and the ability to remain independent of ventilatory support at 18 months of age.

The open-label, dose-comparison, multi-center Phase 1 trial known as STRONG is designed to evaluate the safety, optimal dosing, and proof of concept for efficacy of AVXS-101 in two distinct age groups of patients with SMA Type 2, utilizing a one-time IT route of administration. The primary outcome measure for patients less than 24 months of age at the time of dosing is the achievement of the ability to stand without support for at least three seconds. The primary outcome measure for patients between 24 months and 60 months of age at the time of dosing is the achievement of change in Hammersmith Functional Motor Scale Expanded from baseline. The secondary outcome measure for both age groups is the proportion of patients that achieve the ability to walk without assistance, defined as taking at least five steps independently while displaying coordination and balance. Developmental abilities, including motor function, will also be evaluated as exploratory objectives.

Learn more about clinical trials

We have exclusive worldwide license agreements to develop and commercialize gene therapy using the AAV9 vector to treat two rare neurological monogenic disorders: Rett syndrome (RTT) and a genetic form of amyotrophic lateral sclerosis (ALS) caused by mutations in the superoxide dismutase 1 (SOD1) gene.

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AveXis Research & Development

Cell and Gene Therapy | Alliance for Cancer Gene Therapy …

What is Cell and Gene Therapy for Cancer?Gene therapy is a technique that uses genes to treat or prevent disease such as cancer by inserting a gene into a patients cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including: replacing a mutated or abnormal gene that causes disease with a healthy copy of the gene; inactivating, or knocking out, a mutated gene that is functioning improperly; and introducing a new gene into the body to help fight a disease.

Cell Therapy is the infusion or transplantation of whole cells into a patient for treatment of an inherited or acquired disease like cancer.

Primary Forms of Cell and Gene Therapies for Cancer Treatment

The long-term goal of cancer cell and gene therapy is to develop treatments that attack only cancer cells, eliminating adverse effects on the body. Furthermore, these therapies have potential for treating other diseases such as cardiovascular, disorders, cystic fibrosis, hemophilia, sickle-cell anemia, muscular dystrophy, diabetes, and Parkinsons. All research in this area, therefore, makes a difference.

About Molecular Medicine

Molecular medicine uses the bodys own cells and genes as both the source and medicine for diseases of all types the basis for all cell and gene therapies.

Molecular medicine began with the identification of DNA in the early 1900s. Progress was slow until the mapping of the human genome in the new millennium and the rapid technological advances that made it possible to isolate and target specific cells and genes.

This field of study explains the fundamental genetic errors that cause diseases like cancer and helps establish a blueprint for good health.

Molecular medicine and advanced technology make it possible to target cancers directly without damage to other parts of the body.

Molecular medicine is also referred to as genetic medicine, gene therapy, targeted therapeutics, genetic epidemiology or individualized medicine.

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Cell and Gene Therapy | Alliance for Cancer Gene Therapy ...

Gene Therapy Market Share Insights – Grand View Research

Industry Outlook

The global gene therapy market sizewas valued at USD 7.6 million in 2017. It is estimated to expand at a CAGR of over 19.0% during the forecast period. Increasing number of molecules in the development phase is expected to stoke market growth. It was projected that in 2016, more than 900 molecules are in the development phase that can prove to be an effective treatment for several incurable diseases, which are generally caused by an error in a single gene.

Increasing gene therapy innovations for cardiovascular and rare diseases treatment is one of the key trends driving the market. Rising focus on development of gene therapy treatment for rare diseases is a result of intensifying competition among market players to consolidate their position in the industry.

Gene therapy involves incorporation of an artificial or a modified gene using modified viral vectors that help deliver the gene at intended site of action or even kill the cell that may cause the disease. This treatment is mostly a one-time treatment or requires very few doses of medication to completely cure the disease.

The method of treatment, which was once considered impossible, has now become a trend among big and small companies. A consequence of this has been an upsurge in the number of successful startups, backed by investors in line with big companies. The trends is poised to continue and boost the growth of the market during the forecast period.

Some novel molecules to be used for gene therapy are set to reach the commercialization stage. The growth of the market is largely dependent on key decisions made by manufacturers such as pricing, regulations, and reimbursement for treatment along with payers who help cover treatment costs. However, concerns regarding unethical use of the therapy can hamper growth prospects, especially in developing countries.

The gene therapy market is witnessing an upswing in innovations in various therapeutic fields of medicine. However, oncology is at the forefront in terms of innovation. On the basis of indication, the cancer segment accounted for the leading share of the overall market revenue in 2017. This is due to the high number of pipeline molecules that were registered over the last three years. Rising prevalence of cancer caused due to genetic mutations is also contributing to the growth of the segment. The genetic disorders segment, however, is anticipated to register the highest CAGR during the forecast period.

There are very few drugs in the market that have been approved by various regulatory bodies across the globe. These drugs are considered to change the treatment methods and regimen for rare and orphan diseases, however, their sky high pricing is limiting their commercial success.

For instance, Glybera, the first drug approved for the treatment of LPLD, was a breakthrough in the medical history. However, the drug couldnt be a commercial success due to high pricing at 1.6 million USD at the time of launch and very low prevalence of the disease (1-2 per a million of population).

In 2016, GlaxoSmithKline got another drug Strimvelis approved by European drug regulatory authority for the treatment of ADA-SCID. Other techniques in R&D are likely to witness a significant growth rate in the forecast years due to proven success of approved drugs.

The key element of gene therapy lies in the delivery of modified gene or functioning gene. Delivery systems used should be able to deliver functioning gene to intended cell target through modified viruses, which are considered the best vectors by scientists as viruses are highly evolved in delivering nucleic acid, bypassing the immune system of the host.

Several viruses such as Adeno-associated virus, retrovirus, lentivirus, and herpes simplex virus are modified in labs and are used as carriers for gene therapy drugs. Adenovirus is the most used viral vector followed by Retrovirus due to their reduced immunogenicity. Each of the viruses has its own disadvantage such as toxicity, limited DNA carrying capacity, etc.

Non-Viral vectors are being developed lately that can reduce or eliminate viral toxicity completely, however, none of the non-viral vectors possess ideal vector properties as of now.

Europehas seen two efficient gene therapy molecules after 2010, one was released in 2012 by UniQure N.V and other by GlaxoSmithKline, which were groundbreaking and were approved by the European regulatory body.

The U.S. is estimated to become a leader in terms of revenue as the country more than 64.0% of clinical trials by various big and small companies in the overall clinial trials. Among emerging economies, Russia and China are expected to be at the forefront of the market by a significant margin as they have two approved drugs in the market that can be used for cancer treatment.

Some of the key players are UniQure N.V, Spark Therapeutics LLC, Bluebird Bio, Juno Therapeutics, GlaxoSmithKline, Celgene Corporation, Shire Plc, Sangamo Biosciences, Dimension Therapeutics, Voyager Therapeutics, Human Stem Cell Institute, Bristol Myers Squibb, and Chiesi Farmaceutici S.p.A.

Due to a large number of pipeline molecules in development and intense competition among companies to augment their revenue growth, the market is projected to tread along a healthy growth track. Most of the startups are attracting capital investments to support their research for new molecules and initiate new product development.

Attribute

Details

Base year for estimation

2016

Actual estimates/Historical data

2014 - 2016

Forecast period

2017 - 2025

Market representation

Revenue in USD Million and CAGR from 2017 to 2025

Regional scope

North America, Europe, Asia Pacific, Latin America, Middle East & Africa

Country scope

U.S., Canada, Germany, U.K., China, Japan, Brazil, South Africa

Report coverage

Revenue forecast, company share, competitive landscape, growth factors and trends

15% free customization scope (equivalent to 5 analyst working days)

If you need specific information, which is not currently within the scope of the report, we will provide it to you as a part of customization

This report forecasts revenue growth and provides an analysis of themarket trends in each of the sub-markets from 2014 to 2026. For the purpose of this report, Grand View Research has segmented the global gene therapy market report on the basis of indication, vector type, and region:

Indication Outlook (Revenue, USD Million, 2014 - 2026)

Cancer

Cardio Vascular Diseases

Infectious Diseases

Genetic Disorders

Neuro Disorders

Others

Vector Type Outlook (Revenue, USD Million, 2014 - 2026)

Viral Vectors

Retrovirus

Adenovirus

Adeno-associated virus

Vaccinia virus

Herpes simplex virus

Others

Non-Viral Vectors

Injection of Naked DNA

Lipofection

Others

Regional Outlook (Revenue, USD Million, 2014 - 2026)

North America

Europe

Asia Pacific

Latin America

MEA

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Gene Therapy Market Share Insights - Grand View Research

What is gene therapy? – Genetics Home Reference – NIH

Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patients cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including:

Replacing a mutated gene that causes disease with a healthy copy of the gene.

Inactivating, or knocking out, a mutated gene that is functioning improperly.

Introducing a new gene into the body to help fight a disease.

Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently being tested only for diseases that have no other cures.

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What is gene therapy? - Genetics Home Reference - NIH

Gene Therapy Manufacturing – The Bioprocessing Summit

Cambridge Healthtech Institute s 3rd AnnualAugust 16-17, 2018

It is an exciting time for gene therapy therapies on the market, encouraging clinical data and a long list of pharma collaborations. Pricing and reimbursement takes a majority of the headlines but equally important is producing these therapies in a scalable, cost-effective and robust way, all the while developing a clear CMC and characterization profile that satisfies the regulators.

Cambridge Healthtech Institutes Gene Therapy Manufacturing meeting takes a practical, case study driven approach to the process development, scale-up and production of gene therapies, tackling key topics such as AAV, lentivirus and retrovirus process development and scale-up, CMO management from early to late-stage development.

Final Agenda

Day 1 | Day 2 | Speaker Biographies

Thursday, August 16

11:30 am Registration Open (Grand Ballroom Foyer)

12:15 pm Enjoy Lunch on Your Own

1:15 10th Anniversary Cake Break in the Exhibit Hall with Last Chance for Poster Viewing (Grand Ballroom)

1:55 Chairpersons Remarks

John Pieracci, PhD, Director, Purification, Biogen

2:00 KEYNOTE PRESENTATION: Challenges and Strategies for the Development of a Robust, Scalable, Cost-Effective Biomanufacturing Process

Sadettin Ozturk, PhD, Senior Vice President, Process and Analytical Development, MassBiologics

The use of viral vectors has increased in recent years, both as gene therapies and as vectors for ex vivo cell therapy products. Industrialization of viral vector manufacturing is maturing as companies tackle problems in process control, scale-up, facility design, characterization and quality, and regulatory considerations. This presentation will examine the current state of the art, emerging technologies and challenges.

2:45 Enabling Industrial Scale Production of Lentiviral Vectors for Gene Therapy

Kelly Kral, PhD, Associate Director, Vector Process Development and Manufacturing, bluebird bio

Lentiviral vectors are an ideal platform for indications requiring long-term, stable expression, but the production processes have historically been limited by scale. As the field has now entered commercialization, there is demand for larger quantities of vector, driving the need for more scalable processes. This presentation will review the development, scale-up, and tech transfer of our suspension-based lentiviral vector process.

3:15 Strategies to Deliver Scalable and Reliable Lentiviral Vector Biomanufacturing

Jeffrey Bartlett, PhD, CSO, Calimmune, Inc.

Large-scale clinical production of lentiviral vectors (LV) using current good manufacturing practice (cGMP) methods comes with significant challenges. We have established the Cytegrity stable cell line system for LV bioproduction and have defined key process, quality and regulatory parameters needed to achieve desired productivity and quality across multiples scales and different bioproduction systems. This approach has allowed the production of LV required for Phase I and II clinical trials, while paving the way for future commercialization.

3:45Evolving Process-Centric Facility Design

Mike Sheehan, MSc, MBA, PMP, Senior Project Manager, DPS Group

Increasingly gene therapy products transitioning from clinical phase to commercial manufacture is driving demand for companies to provide additional capacity. Bringing products to market requires exploring opportunities for leading edge facility design, implementing new & evolving technologies, responding to scalability, speed to market and financial considerations.

4:00 Refreshment Break (Foyer)

4:15 Scalable Lentiviral Vector Production Using HEK293 Suspension Cells

Parminder S Chahal, Research Officer, Human Health Therapeutics Research Centre, National Research Council Canada

We have developed expertise in the production of lentiviral vectors (LV) using packaging cell lines and stable producers. Both grow in suspension and in serum-free conditions. Using a stable producer cell line that produces LV expressing GFP, we have compared different modes of operation in bench-scale bioreactors (batch, fed-batch and perfusion). Next, a battery of filters and supplements were evaluated for clarification. A maximal recovery of 78% was obtained.

4:45 Development and Characterization of Novel Micro-RNA Attenuated Oncolytic Herpes Simplex Viruses

Jonathan Platt, PhD., Senior Research Scientist, CMC Operations, Oncorus

Oncorus is developing next generation HSV-based oncolytic virus with enhanced potency for tumor cell killing and recruitment of the immune system. Our innovative miR-attenuation strategy enables robust viral replication in tumor cells, while preventing replication in healthy tissue. The development and characterization of therapeutic oHSV requires thorough product understanding gained through process characterization. Strategies for development and characterization of manufacturing processes centered around a strong organizational infrastructure will be presented.

5:15 End of Day

Day 1 | Day 2 | Speaker Biographies

FRIDAY, AUGUST 17

8:00 am Registration Open and Morning Coffee (Grand Ballroom Foyer)

8:25 Chairpersons Remarks

Nathalie Clment, PhD, Associate Director and Associate Professor, Powell Gene Therapy Center, Pediatrics, University of Florida

8:30 FEATURED PRESENTATION: rAAV Vector Design, Capsid Directed Evolution and Scale Up Activities Using the BEVS System

Jacek Lubelski, PhD., VP, Global Pharmaceutical Development, uniQure

9:00 Towards a Pivotal Process for AAV Manufacture with HSV

David Knop, PhD, Executive Director, Process Development, AGTC

9:30 Large-Scale Manufacturing of Clinical Grade AAV in the Academic Setting

Nathalie Clment, PhD, Associate Director and Associate Professor, Powell Gene Therapy Center, Pediatrics, University of Florida

The talk will present our current methods for the production of research and clinical-grade rAAV with a special emphasis on the HSV-based suspension method capable of generating high titers of improved rAAV quality. Up-to-date in vitro, in vivo, and clinical data will be shown, and pros and cons of the method will be discussed in comparison to the two other most common methods, transfection and the baculovirus system.

10:00 Networking Coffee Break (Foyer)

10:30 Scale-Up Approach to AAV Manufacturing

Johannes C.M. van der Loo, PhD, Director, Clinical Vector Core, The Raymond G. Perelman Center for Molecular and Cellular Therapies, Childrens Hospital of Philadelphia

The Clinical Vector Core at the Childrens Hospital of Philadelphia manufactures preclinical- and clinical-grade AAV for academia and industry-sponsored clinical trials. With the field of gene therapy maturing, there is a growing need for larger scale products. We will discuss a strategy for scale-up that builds on our existing mammalian adherent cell-based manufacturing platform.

11:00 Virus-Like Particles and Other Extracellular Particles from Insect and Mammalian Cells

Alois Jungbauer, PhD, Professor, Institute of Biotechnology, University of Natural Resources and Life Sciences (BOKU)

Virus-like particles and other extra cellular particles are a next generation of biopharmaceuticals. They can be produced by a wide variety of host cells. The challenge is the production of high titers and downstream processing. The particle of interest are contaminated with other particles with similar biophysical properties and therefore difficult to separate. Examples will be given for 3 different cell types.

11:30 Considerations for the Purification Process Characterization of an AAV from Recovery to Drug Substance

Ratish Krishnan, PhD, Scientist, Bioprocessing Research & Development, Pfizer

Smart and efficient approaches for lab-scale characterization are required to ensure a robust adeno-associated manufacturing process. Specific challenges related to the uniqueness of characterizing an AAV manufacturing process will be discussed. Focus will be given to working with limited quantities of material and employing assays that are still being defined.

12:00 pm Next Generation AAV Viral Vector Manufacturing: Proven Technologies with a Modern Twist

Sandhya Buchanan, Director, Upstream Process Development, FUJIFILM Diosynth Biotechnologies

Current approaches to commercial-scale manufacture of viral vectors have been successful for many early phase trials and some late phase trials. Unique challenges/limitations arising for AAV manufacturing include quantities sufficient for patient needs and consumables for manufacturing. We discuss proven technologies blended with modern advancements to meet the needs of the advancing field of gene therapy.

12:30 Enjoy Lunch on Your Own

1:25 Chairpersons Remarks

Chia Chu, Senior Principal Scientist, Bioprocess Research & Development, Pfizer

1:30 FEATURED PRESENTATION: Separation of Full and Empty AAV Particles Using Scalable Isocratic Elution Chromatography

Meisam Bakhshayeshi, PhD, Head, Purification Development, Gene Therapy, Biogen

Robust and efficient removal of AAV empty particles is a critical part of the AAV manufacturing process. In this study, we present a scalable ion exchange chromatography process with isocratic wash and elution to separate full and empty particles. A combination of mono- and di-valent salts were used as eluents to achieve the high degree of resolution required for this separation. High product purity and recovery was achieved from this process.

2:00 Lyophilisation of AAV Gene Therapy Product

Tanvir Tabish, PhD, Head, Drug Product Development for Gene Therapy, Device and Combination Products, Shire

The gene therapy adeno-associated virus (AAV) subtype 8 containing Factor IX (FIX)(BAX335) was formulated in a new proprietary buffer and lyophilized. A stability study was established with the lyophilized material to determine its stability profile at the accelerated temperature of +5C over a 10 month period. The freeze-dried product displayed an improved stability profile when stored at a temperature of +5C. We demonstrated the feasibility of lyophilisation of the AAV viral drug product in the formulation buffer.

2:30 AAV Manufacturing at 2,000L Scale

Alex Fotopoulos, PhD., Senior Vice President, Technical Operations, Ultragenyx.

Changing the manufacturing site (tech transfer) should always include an assessment of comparability, however the ability to demonstrate this varies between early and late development. This talk will discuss common pitfalls and mistakes and highlight key aspects of the comparability exercise.

3:00 CMO Selection for Cell & Gene Therapy

Chad Green, PhD, Principal & Senior Consultant, Dark Horse

As the diversity of CMOs available for cell and gene therapies continues to grow worldwide, identifying the most suitable to engage is becoming an increasingly complex challenge. This presentation will address fundamental questions, such as whether a CMO is even the best choice for manufacturing before progressing to provide concrete guidance on the critical questions to ask prospective CMOs (and yourself), how to ask them and how to analyze the answers and make an optimal, rational choice.

3:30 Close of Conference

Day 1 | Day 2 | Speaker Biographies

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Gene Therapy Manufacturing - The Bioprocessing Summit

The Gene Therapy Plan: Taking Control of Your Genetic …

Praise for The Gene Therapy PlanA guide to harnessing the power hidden in food to subvert a genetic predisposition for disease. . . . Gaynors informative tome is worth reading. Publishers Weekly

The Gene Therapy Plan identifies how the lives we lead, and in particular, the foods and nutritional supplements we ingest, are a key determining factor in whether latent disease (which most people have to some degree) materialize or stay dormant. By identifying researched nutritional protocols that target specific conditions, and by providing a range of rich case studies from his practice as a leading oncologist and internist, Dr. Gaynor provides insight and an action plan into how the body operates that will benefit medical practitioners and patients alike. Deepak Chopra, M.D.The Human Genome Project promised to create a new era of genetic medicine, new drugs, and therapies to advance human health. But the real awakening has been the understanding of foodreal whole foods, herbs, phytonutrientsas medicine and how it can literally upgrade your biologic software by improving the expression of your genes.In The Gene Therapy Plan Dr. Gaynor makes the healthcare of the future available to you today. If you want to learn how to use food and nutrients to prevent and even reverse most chronic disease, read this book! Mark Hyman, M.D., Director of the Cleveland Clinic Center for Functional Medicine and author of the #1 New York Times bestseller The Blood Sugar SolutionThe Gene Therapy Plan is a comprehensive and practical approach to the science of epigeneticsand how to apply it to your life right now. This book is a godsend that could save your life. Christiane Northrup, M.D., author of the New York Times bestseller Womens Bodies, Womens WisdomA brilliant and important piece of work from one of our most distinguished and creative medical thinkers. Do yourself and your family a huge favor: Read this phenomenally important book and learn why and how you can live a healthier life. Devra Davis, Ph.D., M.P.H., founder and president of the Environmental Health Trust, author of The Secret History of the War on CancerDr. Gaynor is a visionary healer. This is a comprehensive, coherent, practical, and easily digestible resource for all who wish to tip the balance away from disease toward health and wellness. Sheldon Marc Feldman, M.D., Vivian L. Milstein Associate Professor of Clinical Surgery, Columbia University College of Physicians and SurgeonsDr. Gaynor presents a comprehensive strategy for readers to re-orient their diet and lifestyle using everyday activities that can help one live longer, and live better. With The Gene Therapy Plan, Dr. Gaynor brings his own integrative philosophy and practice to readers in an engaging and actionable way. William Li, M.D., president and medical director of The Angiogenesis FoundationDr. Gaynor has and always will be at the forefront of integrative medicine. The Gene Therapy Plan empowers you to take control of your health and life. Mimi Guarneri, M.D., president of the Academy of Integrative Health and Medicine

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The Gene Therapy Plan: Taking Control of Your Genetic ...

GeoGene: Gene Therapy, What it is, The process and Vectors …

What is Gene Therapy?

Certain diseases are caused byfaulty genes which produce defective proteins. The symptoms of genetic disease are the result of subsequent disrupted vital cell processes caused by missing or defective proteins. In theBio Building Blockssection of this web-site, protein synthesisis outlined as the process whereby,genesultimately give rise toproteinswhich are responsible for important cell processes. If a particular gene is defective, its protein product may not be made at all, may work poorly or may behave too aggressively.

For example:Cystic Fibrosis(CF) is caused by amissing or mutated genethat results in adefective cell membrane transport protein. This ultimately results in a build-up of thick mucus in the lungs and the body's airways.As another example,cancersare caused by cells that divide and grow uncontrollably.Particular genes can cause such cell growth to occur if they are defective. Such defective genes are calledoncogenes.

Are we treating the symptom or treating the cause? Historically, genetic disorders have been treated byaddressing the biological eventsthat result from the genetic mutation, as opposed tofixing a defective gene(or genes) the ultimate source of the problem.For example, the treatment of diabetes has historically involved the administration of insulin (a protein), instead of fixing the defective genes in pancreatic cells that actually prevent these cells from producing insulin in the proper amounts, on their own.

Gene therapy is an alternative approach whereby a genetic disorder is treated by inserting or integrating new genes into human cells. Many attempts at gene therapy aim to add a useful gene into a selected cell type to compensate for a missing or defective version. Other efforts aim to instill new properties in the target cell. This latter method is often employed in the treatment of cancer, where toxic genes are added to cancer cells in an effort to eliminate them.For an overview of how a specific gene is located and isolated from its source (so that it can be introduced into the patient) see ourGenetic Engineeringsection.

It should be noted that even the most advanced somatic cell therapy techniques are still in clinical trials, and are not yet approved for general application. Much more research is required to develop safe, reliable gene therapy techniques.

Depending on the cell types affected, gene therapy can be classified into two broad categories: germ-line gene therapy and somatic cell gene therapy.Germ-line therapyoccurs when germ cells (reproductive cells) are altered, meaning that the resultinggenetic changes will be passed on to the patient's offspring. Alternatively,somatic cell gene therapyinvolves the alteration of somatic cells (non-reproductive body cells, like skin, brain or muscle cells). This genetic manipulation willonly affect the individualto which the changes were made. Somatic cell gene therapy is the only type presently being considered in humans.

Suppose a patient is afflicted with a genetic disorder that affected only certain cells in her or his brain. How could she or he be treated using gene therapy so that the therapeutic gene targets only those cells affected by the disorder? One solution is through the use of avector. A vector is simply a "transporter" for the genetic material that allows it to enter the target cell and, depending on the vector type, can cause new genes to be integrated into the host cell genome. Vectors must be administered totarget specific cell types.

There are three principal ways in which vectors can be administered to carry new genes into target cells. The first is calledex vivosomatic gene therapy, wherethe target cells are removed from the body, cultured in the laboratory with a vector, and re-inserted into the body. This process is usually carried out using blood cells because they are the easiest to remove and return.

The second option,in situsomatic gene therapy, occurs when thevector is placed directly into the affected tissue. This process is being developed for the treatment of cystic fibrosis (by direct infusion of the vector into the bronchi of the lungs), to destroy tumours (eg: brain cancer), and for the treatment of muscular dystrophy.

The third option isin vivosomatic gene therapy, where thevector is injected into the bloodstream, and is able to find and insert new genes only into the cells for which it was specifically designed. Although there are presently noin vivotreatments available, a breakthrough in this area will make gene therapy a very attractive option for treatment.In this case the vector designed to treat our hypothetical patient could be injected into a blood vessel in her or his arm and would find its way to the affected brain cells!

Vectors used in gene therapy can be classified as eitherviralornon-viral.

BothDNAandRNAviruses are being developed as vectors for use in gene therapy. Viruses are an excellent choice for use as vectors, because they have gained, through long periods of evolution, the ability to avoid destruction by the human immune system, and the capacity to get their own genetic material inside human cells. As discussed in theBio Building Blockssection, viruses consist of genetic material (DNA or RNA) surrounded by a protective coat made of proteins and occasionally other molecule types as well.

Normally, a virus infects a cell when its genetic material enters it. Once the viral genetic material is inside, it "hijacks" the cell's DNA- and protein-making machinery, causing it to produce new viruses. Some viruses are even capable of integrating their own genetic material into the host cell's genome.

It is the outer protective viral coat that allows the inner genetic material to penetrate the cell. This outer coat also determines the type of cell that a given virus will infect. Once inside, it is the harmful viral genes that actually hijack the cell and eventually cause it to die.

To trick the virus, scientists retain the outer viral coat, but modify the inner genetic material. They remove the harmful genes and replace them with therapeutic ones. Now the virus ispathogenically disabled(it is no longer harmful to the cell it infects) and incapable of reproducing itself. However, it retains its capability to transfer its genetic material to the cells for which its outer coat was designed.The transfer of genetic material by way of a viral vector is calledtransduction.

The structure and mode of infection of retroviruses is discussed in theBio Building Blockssection. Briefly, retroviruses have RNA as their genetic material. These viruses also carry a specialenzymethat, once inside a cell, makes double-stranded DNA from the virus' RNA template. The new DNA becomes incorporated into the host cell's genome. When the "new" chromosomal genes are transcribed, new virus particles are made, which will leave the cell to infect other cells.

Most types of retroviruses are not very harmful to the cell. Even though allviruses to be used as vectors are deactivated,' meaning that their harmful genes are removed, the fact that the types of retroviruses presently being used as vectors are not very harmful in their natural forms means that their use poses less risk than the use of some other viruses. Even if something goes wrong and some of the original retrovirus particles are administered to the patient, they will not cause serious problems.

Themurine leukaemia virus(MuLV) is one of the more popular retroviruses used as a retroviral vector. The reproductive genes in the retrovirus are replaced with the therapeutic gene. When the virus infects the cell,the therapeutic gene gets incorporated into the cell chromosomes. The new gene causes a protein to be produced which is hoped to have some positive therapeutic effects, either providing an otherwise missing protein, or causing the destruction of harmful cells.

There are several challenges that scientists must overcome for effectivein vivotreatment of disease using retroviral vectors. For example, theviruses must be capable of targeting only those cells affected by the disorder. If this were the case, they could be injected directly into the bloodstream (in vivogene therapy) where they would become dispersed throughout the body, but would only transduce those cells for which they were designed. Presently, retroviral vectors are not terribly specific, meaning that many cells not intended for the transfer of the gene are transduced by the virus, which reduces the transfer to the targeted cell population.

To understand how viruses can be made to be more specific, we should considerhow viruses "choose" the cells they infect. A virus must bind to specific surface receptor molecules to gain entry into a cell. To this end, retroviruses have outer envelope proteins that fit perfectly into certain receptors on specific cells. The MuLV virus binds to cells containing a receptor called theamphotropic receptor. The problem is that a broad range of cell types possess the amphotropic receptor. This means that the MuLV virus, in its natural form, can infect all of these cell types, most of which are likely not the target of the therapy!

To make retroviral vectors more specific about the cells they invade, scientists are experimenting with ways ofreplacing or modifying the outer viral proteins, so that they fit into more rare receptors that appear only on specific cell types being targeted for therapy.Another approach has been toadd new proteinsto the outer viral envelope which either better recognize the target cell, or better recognize the region of the body where the target cells are located.

Another challenge is toengineer retroviral vectors to transducenon-dividingcells. Most retroviruses target actively dividing cells, which makes them ideal for the treatment of rapidly dividing tumour cells, but not in situations where a therapeutic gene is to be introduced into a non-dividing cell, like in the treatment of cystic fibrosis mentioned above. Those few retroviruses that have the ability to infect non-dividing cells are the harmful ones (HIV, the virus that results in AIDS, is one of them). HIV viruses (with their harmful genes removed) cannot be used as vectors, because even with the removal of these genes, there is still a possibility that the virus might become harmful again through a process called recombination. To virtually eliminate the possibility that harmful viruses are produced in this way, while still harnessing the capability of HIV to transduce non-dividing cells, scientists are experimenting with the development of hybrid vectors, made up mostly of other retroviruses and which contain very small and harmless parts of the HIV virus.

As of April, 1998, there was only one vector-based therapeutic technique in the final clinical trial stage(called Phase III). This technique employs a retroviral vector called G1TkSvNa for the treatment ofglioblastoma multiforma, a malignant brain tumour. The treatment is an in situ therapeutic technique, where mouse cells capable of producing and secreting the vector are injected into the tumour.The secreted vectors infect only those cells that are rapidly dividing, meaning only the tumour cells and the vessels supplying blood to the tumour are transduced. The gene transduced into the tumour cells gives rise to a protein (calledHerpes Simplex Thymidine Kinaseor HSTk).Fourteen days later, a drug called ganciclovir is injected into the patient, which is toxic to any cell that incorporates it into its DNA. Only the cells containing HSTk (the tumour cells) are capable of incorporating ganciclovir into their DNA and these cells are therefore selectively killed off.

Adenoviruses are DNA viruses that are able to transduce a large number of cell types, including non-dividing cells. Adenoviruses also have the capacity to carry long segments of added genetic information. In addition, it is fairly easy to produce large amounts of adenoviruses in culture. Adenoviruses, in their natural form, are not very harmful, typically causing nothing more serious than a chest cold in otherwise healthy people. This means that their use as vectors is quite safe. For all these reasons, adenoviruses are currently the most widely used DNA vectors for experiments inin situgene therapy.Research is currently under way using adenoviral vectors for the treatment of several cancers and cystic fibrosis.

The size of the adenovirus protein coat is just large enough to fit the original viral DNA inside. As a result, for every new therapeutic gene to be inserted into the viral genome, a corresponding piece of the old viral DNA must be removed.To make room for the new therapeutic DNA, a region of the old viral DNA called E3 is sometimes removed. However, removing the E3 region has drawbacks, because it codes for a protein that suppresses the human immune response against the vector. Without the E3 region, the virus is more susceptible to the immune system and is more likely to be destroyed before it has served its purpose.

Adenoviral vectors send their DNA to the nucleus, butthe DNA does not get incorporated into the host cell's chromosomes. For this reason, the viral DNA has a finite lifetime within the cell before it is degraded, meaning that the added genes are effective only temporarily. Treatments for chronic conditions like cystic fibrosis, therefore, would need to be repeated periodically, perhaps on a monthly or yearly basis. On the other hand, the transient nature of therapeutic gene expression is useful when the added genes are needed temporarily to induce an immune response to a cancer or pathogen.

Among the other virus types being explored as vectors are theadeno-associated virus(AAV) and theherpes simplex virus(HSV). Both are DNA-based viruses. AAV integrates its genetic material into a host chromosome and cause no diseases in humans. However, because AAV are small, they cannot accommodate large genes. HSV vectors do not integrate their genes into the host genome. They tend to target neurons and thus have the potential for use in the treatment of neurological disorders.

The use of non-viral vectors can involve a direct injection ofplasmid DNAor mixing plasmid DNA with compounds that allow it to cross the cell membrane and protect the DNA from degradation. These methods are currently less efficient than the use of viral vectors. However, unlike disabled viruses which have the possibility of changing spontaneously and causing disease, non-viral vectors possess no viral genes and therefore cannot cause disease.

Liposomes are small, hollow spheres of fatty molecules that are capable of carrying DNA inside of them.A liposome can fuse with the cell membrane, releasing its contents into the cell interior.

Plasmid DNA containing the therapeutic gene is incubated with the empty liposomes under specific conditions. The negatively charged DNA binds to the positively charged (calledcationic) liposomes and the plasmids are absorbed. Liposomes containing plasmid DNA are calledlipoplexes.The lipoplexes can subsequently enter the cells of interest, and thus introduce the therapeutic DNA into the cells.

Experiments have been carried out where lipoplexes have been injected into tumours. The lipolexes contained a gene that gives rise to a protein that is recognized by the human immune system. Theoretically, thesegenes should cause the tumour cells to express the recognizable protein on their surface, which will mark the cells for destructionby the immune system.

The use of lipoplexes for the treatment of cystic fibrosis is currently being studied as well. The cause of the illness is a defective gene which causes a particular protein in the patient's lung cells to be defective. The lipoplexes that are administered using an aerosol spray into the patient's lungs, contain the gene for a functional version of the protein.

Lipoplexes are not as efficient as viral vectors in introducing genes into cells. To improve their efficiency, scientists are attempting to incorporate some viral proteins into the outer surfaces of lipoplexes. In particular, the viral proteins that recognize and bind to specific molecules on the host cell's surface, are being incorporated.

Muscle cells have been shown to be capable of taking up and expressing plasmid DNA. This raises the possibility that plasmid DNA injected into muscles could stimulate the production by muscle cells of a therapeutic protein. This protein could then be secreted into the bloodstream and to the rest of the body. For example, the gene coding for erythropoietin (a protein which helps stimulate the production of red blood cells) has been experimentally injected into animal muscles with some success. Such a treatment would be useful to patients after chemotherapy or radiation therapy.

In addition,plasmid DNA shows promise for use in vaccines, stimulating protective immune responses against diseases like herpes, AIDS or malaria. When the plasmid DNA is injected into muscles, it enters muscle cells and as a result, causes the cells to produce the proteins that correspond to the genes the plasmids contain. The immune system will then learn to recognize the new proteins and will destroy them if they are encountered in the future. Experiments are currently under way where plasmids containing genes for viral coat proteins are injected, in attempt to make the immune system recognize these viruses, so that it will attack and destroy them if they are ever encountered.

As discussed in theBio Building Blockssection, viruses hijack cellular machinery to produce their own proteins and to replicate their genetic material, which results in the production of new viruses.One of the potential uses of antisense technology is to prevent viruses that infect a host cell from producing their own proteins. This would, in turn, prevent their replication.

Recall that proteins are constructed through atwo step process. In the first step,DNA is transcribed to produce messenger RNA(mRNA). The second step involves thetranslation of the mRNA to make a protein. Antisense drugs interact with mRNA, preventing them from being translated into their corresponding protein.

An mRNA molecule is a chain of nucleotides, that gets "read" by a ribosome in the synthesis of a protein. An antisense drug is anoligonucleotide(a relatively small, single stranded chain of nucleotides) that iscomplementaryto a small segment of a target mRNA molecule. When the drug comes into contact with its complementary mRNA, it binds to the mRNA in the same way as the two strands of a DNA molecule bind together.This makes the mRNA "unreadable" by the ribosome, and so no protein is produced.

Because an antisense drug is designed to be complementary to a particular mRNA sequence that is specific to a particular virus' mRNA, it will not interfere with any of the host cell's naturally produced mRNA, meaning that the side effects of the drug are minimal.

At the end of August, 1998, the US Food and Drug Administration (FDA) approved a drug calledformivirsenfor the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS.This makes formivirsen the first antisense drug on the market.Formivirsen blocks the replication ofcytomegalovirus(CMV) which causesretinitis, an eye infection leading to blindness that mainly affects AIDS patients. The drug is periodically injected into the patient's eye, and is claimed to cause only mild side-effects as compared to some other antiviral drugs.

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GeoGene: Gene Therapy, What it is, The process and Vectors ...

Antiviral Gene Therapy Research Unit – Wits University

Welcome to the Antiviral Gene Therapy Research Unit (AGTRU) of the University of the Witwatersrand and South African Medical Research Council (SAMRC)

Investigation by the AGTRU team is focused on countering viral infections that cause serious health problems in South Africa. The long term objectives of AGTRU are to

Discovery of the RNA interference (RNAi) pathway and advances in the engineering of sequence-specific nucleases have provided the means for powerful and specific disabling of genes. These advances led to considerable enthusiasm for use of gene therapy to counter viral infections, such as are caused by persistence of hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1). The focus of the AGTRU has been on optimising use of RNAi activators and transcription activator-like effector nucleases (TALENs) to inhibit viral proliferation. Development of suitable vectors for delivery of antiviral sequences to infected cells is also an active field of investigation within the unit.

Research activities are generously supported by South African and International funding agencies. South African and international partnerships have been established, and these are an important contributor to the groups resource base.

The unit currently has approximately 20 members and these include molecular biologists, clinicians and postgraduate students. There are four tenured university appointees in the unit and the director is Professor Patrick Arbuthnot. AGTRU is equipped as a modern molecular biology research laboratory and has expertise in a range of techniques. These are advanced methods of nucleic acid manipulation, gene transfer to mammalian cells, use of lipoplex and recombinant viral vectors. AGTRU is set up to investigate efficacy of antiviral compounds in vivo in murine (e.g. HBV transgenic mice) and cell culture models of viral replication.

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Antiviral Gene Therapy Research Unit - Wits University

Gene Therapy Research | Ophthotech

Gene Therapy Research Programs

Ophthotech initiated an innovative gene therapy program focused on applying novel gene therapy technology to discover and develop new therapies for ocular diseases. We intend to investigate promising gene therapy product candidates and other technologies through collaborations with leading companies and academic institutions in the United States and internationally.

As we evaluate the unmet medical need for the treatment of orphan ophthalmic diseases, we have considered that many of these diseases are caused by one or more genetic mutations and currently have no approved treatment options available. Further, the potential to achieve an extended treatment effect and possibly a cure through a single gene therapy administration is particularly appealing to patients who do not have any treatment options, as well as for patients with age-related retinal diseases who currently require chronic therapy over years, if not decades.

Gene therapy consists of delivering DNA encoding for a functional protein to a target tissue to facilitate protein synthesis using a recipients existing cellular machinery. Gene therapy can be used to replace a non-functional protein produced innately by the subject as a result of a genetic mutation or simply as a means of producing and delivering a therapeutic protein that would not otherwise be produced within the body. The DNA, which is generally delivered by a viral vector, is governed by a promoter sequence which controls transcription of the gene of interest, or transgene, into RNA to initiate protein synthesis. Some of the challenges that gene therapy faces are producing vectors that transfect, or deposit the transgene, in only specific cell types, producing the desired protein at the therapeutic dose levels, and avoiding inducing an inflammatory response that leads to tissue damage. We are particularly interested in adeno-associated virus, or AAV, gene therapy delivery vehicles, as AAV vectors are relatively specific to retinal cells and their safety profile in humans is relatively well-documented as compared to other delivery vehicles and gene therapy technologies currently in development.

University of Massachusetts Medical School and its Horae Gene Therapy Center

For our first gene therapy collaboration, we entered into a series of sponsored research agreements with the University of Massachusetts Medical School (UMMS) and its Horae Gene Therapy Center to utilize their minigene therapy approach and other novel gene delivery technologies to target retinal diseases. As a condition of each research agreement, UMMS has granted the Company an option to obtain an exclusive license to any patent or patent applications that result from this research.

The use of minigenes as a novel therapeutic strategy seeks to deliver a shortened but still functional form of a large gene packaged into a standard-size AAV delivery vector commonly used in gene therapy. The minigene strategy may offer an innovative solution for diseases that would otherwise be difficult to address through conventional AAV gene replacement therapy where the size of the gene of interest exceeds the transgene packaging capacity of conventional AAV vectors. Research in this newly evolving area of gene therapy is led by Prof. Hemant Khanna and colleagues in the Horae Gene Therapy Center and was described in a recent journal article in Human Gene Therapy, Gene Therapy Using a miniCEP290 Fragment Delays Photoreceptor Degeneration in a Mouse Model of Leber Congenital Amaurosis by Wei Zhang, Linjing Li, Qin Su, Guangping Gao, and Hemant Khanna, all at the University of Massachusetts Medical School.

The collaboration with UMass Medical School will also focus on developing the next generation of gene therapy vectors to allow novel delivery approaches for treatment of retinal diseases.

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Gene Therapy Research | Ophthotech

Gene Therapy – Genetics Generation

What is Gene Therapy?

Gene therapy is a technique used to correct defective genes genes that are responsible for disease development. Specifically, according to the American Society of Gene and Cell Therapy-

Gene therapy is defined as a set of strategies that modify the expressionof an individuals genes or that correct abnormal genes. Each strategyinvolves the administration of a specific DNA (or RNA).

Gene therapy is the manipulation of the expression of specific genes in a persons body, in hopes of treating a disease or disorder. Gene therapy is still considered experimental and only available via clinical trial. Although many successful trials have been documented (see Interesting Links below), gene therapy has a checkered history. In some gene therapy trials, there were cases of leukemia as an unintended side-effect, and even cases of death (see link on Jesse Gelsinger below).

Image courtesy of Wikimedia Commons

How Does Gene Therapy Work?

Although there are several strategies for gene therapy, the most commonly used method involves inserting a therapeutic gene into the genome to replace the abnormal or disease-causing gene. The gene that is inserted is delivered into a target cell via a vector. Usually, this vector is a virus, although non-viral vectors are in development. Viruses are a good choice for introducing genes into a cell because they typically operate by transferring their own genetic material while replicating themselves. Once target cells are infected with the viral vector, the vector releases its therapeutic gene which then incorporates into the cells DNA. The goal is that the cell will start using the new gene to make functional, healthy proteins.

There are three main strategies for using gene therapy to restore the target cells or target tissues to a normal, healthy state.

1. Insert the functional version of a gene in hopes of replacing the abnormal form. This is used to treat single-gene disorders like hemophilia A and B and cystic fibrosis.

2. Insert a gene that encodes for a therapeutic protein that treats a disease. This is used to treat acquired diseases likeinfection or ischemic heart disease.

3. Use gene transfer to down-regulate gene expression in hopes of decreasing the activity of a harmful gene.

Current Areas of Research

Although gene therapy is still experimental, many diseases have been targets for gene therapy in clinical trials. Some of these trials have produced promising results. Diseases that may be treated successfully in the future with gene therapy include (but are not limited to):* Anemias* Cardiovascular diseases* Cystic Fibrosis* Diabetes* Diseases of the bones and joints* Eye disease and Blindness* Gauschers Disease* Hemophilia* Huntingtons Disease* Lysosomal storage diseases* Muscular Dystrophy* Sickle cell disorder

The main challenges facing gene therapy are the identification of disease causing genes, the targeted delivery of the therapeutic gene specifically to the affected tissues, and the prevention of side effects (such as an immune response) in the patient.

Gene Therapy for Enhancement Purposes

If gene therapy becomes routine medical practice, then it is reasonable to believe that some will seek it out for enhancement purposes. For example, a gene therapy designed to help patients with Alzheimers disease may be appealing to a normal individual hoping to boost memory. One potential area of enhancement that has been discussed is gene doping in sports. Gene doping is defined by the World Anti-Doping Agency (WADA) as the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance. The purpose of gene doping is toenhancea given gene rather thancorrecta faulty one. Potential targets of gene doping include:

* Erythropoietin (EPO) for increased production of red blood cells* Insulin-like Growth Factor-1 gene for increased muscle mass* Myostatin for increased muscle mass* Vascular Endothelial Growth Factor (VEGF) for an increase in blood flow

This form of doping would be hard to detect because the doping substances are produced directly in an individuals own cells after these genes with performance-enhancing effects have been expressed. Whether or not to use gene therapy in the future for enhancement purposes, and how to regulate it, will require a complex discussion of ethics in which there will likely be many differing opinions.

Interesting Links*The American Society of Gene and Cell Therapy* National Geographic articleon gene doping* Science Daily article onrecent gene therapy news* New York Times article on the death of Jesse Gelsinger* Scientific American article on treating blindness with gene therapy

CLICK HERE to read our case study involving ethical issues associated with gene therapy

REFERENCES

Gene Therapy and Cell Therapy Defined. American Society of Gene and Cell Therapy, n.d. Web. 04 Nov. 2012. .

Gene Therapy..Human Genome Project Information, n.d. We. 04 Nov. 2012.

Pawliuk R et al. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science. 2001; 294:2368-2371.

Unal M, Unal DO. Gene doping in sports. Sports Medicine. 2004; 34:357-362.

Wells DJ. Gene doping: the hype and the reality. British Journal of Pharmacology. 2008 January; 154: 623-631.

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Gene Therapy - Genetics Generation

Gene Therapy Clinical Research – nationwidechildrens.org

Purpose of Study

The Newcastle University and the University of Rochester, in collaboration with the United States National Institutes of Health, and the National Institute of Neurological Disorders and Stroke, are conducting a phase III study with corticosteroids in boys with Duchenne Muscular Dystrophy (FOR DMD study).

Corticosteroids are currently the only medicine that has been shown to increase muscle strength in boys with DMD. Doctors have tried different ways of prescribing corticosteroids in order to decrease undesirable side effects. Currently, different doctors in different countries prescribe the drugs in different ways, and some do not prescribe corticosteroids at all.

The FOR DMD study aims to compare three ways of giving corticosteroids to boys with DMD to determine which increases muscle strength the most, and which causes the fewest side effects.

Using the results of this study, we aim to provide patients and families with clearer information about the best way to take these drugs.

This study will look at three ways of taking corticosteroids by the mouth:

All three dosages are commonly used in boys with DMD and have shown to be beneficial.

In this study there is no placebo group, which means that all participants will receive active drugs (Prednisone or Deflazacort). However, neither the boys nor the clinicians will know which treatment or regime the boy is taking.

The study will recruit 300 boys around Europe, United States and Canada.

In North America, 16 centers will take part in the study:

Patients who do not attend one of these hospitals for their routine follow-up can also participate, but will have to travel to their closest participating site to receive the study drug and for the check-ups.

Participants will receive study medication for a minimum of three years and a maximum of five years (depending on how early the boy was recruited into the study) and participation involves visits to the study hospital every three months for the first 6 months and every six months thereafter. At these visits we will be repeating many of the tests your child usually has in clinic for his routine DMD follow up.

Who can participate:

In order to take part in the study boys need to fulfil a number of criteria. These can only be checked when you come into the clinic. However, at this stage if your child may be eligible if he:

Who to contact:

If you feel that your child might be able to participate in this trial, please feel free to discuss it with your doctor locally. Alternatively, if you would like further information, please contact the University of Rochester Medical Center: Kim Hart | Phone: 1 (585) 275-3767.

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Gene Therapy Clinical Research - nationwidechildrens.org

The Cancer Gene Therapy Research Team | Kids Research

> Dr Geoffrey McCowage, Cancer Gene Therapy Group Leader

Geoffisa Paediatric Oncologist at The Children's Hospital at Westmead and a member of Sydney Cell and Gene Therapy (SCGT). He is a Principal Investigator for clinical trialswithin the Children's Oncology Group. He has a particular clinical interest in neuro-oncology and sarcomas of bone and soft tissue. Dr McCowage leads the clinicaland translational researchof the Cancer Gene Therapy group.

> Dr Belinda Kramer,Cancer Gene Therapy Group Co-Leader, email: belinda.kramer@health.nsw.gov.au

Belinda is a senior research scientist and leadslaboratory research within the Cancer Gene Therapy Group. She is also a member of Sydney Cell and Gene Therapy (SCGT) and highly experienced in genetransfer techniquesand cell therapies.

> Dr Kenneth Hsu, Senior Post-doctoral Research Officer, Cancer Gene Therapy Group Co-Leader, email: kenneth.hsu@health.nsw.gov.au

Ken is an experienced post-doctoral scientist working on the development of novel vectors for gene modification of T cells to target tumours and the development of clinically applicable T cell manufacturing methodology for the project.

> Other Research Team Members

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The Cancer Gene Therapy Research Team | Kids Research

World Gene Therapy Research Report 2018: Technologies …

DUBLIN--(BUSINESS WIRE)--The "Gene Therapy - Technologies, Markets and Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's 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. Gene editing technologies such as CRISPR-Cas9 and CAR-T cell therapies are also included

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 2016, over 2050 clinical trials were completed, were ongoing or had been approved worldwide. A breakdown of these trials is shown according to the geographical areas and applications.

The markets for gene therapy have been difficult to estimate as there only a few approved gene therapy products. Gene therapy markets are estimated for the years 2017-2027. 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.

The voluminous literature on gene therapy was reviewed and selected 750 references are appended in the bibliography. The references are constantly updated. The text is supplemented with 78 tables and 25 figures.

Profiles of 183 companies involved in developing gene therapy are presented along with 250 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 in 2 decades. 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

Executive Summary

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, Ethical Patent 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 https://www.researchandmarkets.com/research/ck3cjd/world_gene?w=4

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World Gene Therapy Research Report 2018: Technologies ...

Operationalizing Gene Therapy Trials – Premier Research

Even measured against the vast scientific mystery that defines the biotech industry, gene therapy poses extraordinary challenges. Its still a young field, the science is stunningly complex, and the regulatory terrain is still evolving.

Sponsors and CROs have an understandably challenging time operationalizing clinical trials for new gene therapy treatments. In this webcast, well examine the history and current state of gene therapy research and investigate the obstacles in both patient recruitment and retention, study start-up regulations, and types of gene therapy vectors and vector delivery strategies.

Lisa Dilworth, Executive Director Program Strategy Rare Disease and Pediatrics, regularly consults with clients on key factors such as study design, eligibility criteria, appropriate patient populations, end point selection and program strategy in order to develop global therapeutic product strategies for rare and pediatric trials. Ms. Dilworths expertise and experience includes multiple gene therapy trials in subjects ranging from neonates to adults around the globe.

Ms. Dilworth holds a masters degree in Clinical Research from the University of California, San Diego and a Bachelors in Biology from the University of California, Berkeley. Her prior work as a study coordinator and various clinical operations roles enable her to work closely with clients, physicians and patients with a variety of disorders.

Nadia Zeini is currently working as Sr. Regulatory Study Start Up Manager at Premier Research since December 2016. She is responsible for all regulatory and start up activities in EU and non-EU countries, as applicable. Nadia Zeini has a solid regulatory background where she grew from local start up associate to Global Regulatory lead for ten years

Ms. Zeini holds a Chemistry-Major in Biochemistry from Complutense University in Spain as well as a Masters degree in Clinical Trials from Universidad of Seville in Spain.

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Operationalizing Gene Therapy Trials - Premier Research

Gene therapy – Mayo Clinic

Overview

Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease.

Genes contain your DNA the code that controls much of your body's form and function, from making you grow taller to regulating your body systems. Genes that don't work properly can cause disease.

Gene therapy replaces a faulty gene or adds a new gene in an attempt to cure disease or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS.

Researchers are still studying how and when to use gene therapy. Currently, in the United States, gene therapy is available only as part of a clinical trial.

Gene therapy is used to correct defective genes in order to cure a disease or help your body better fight disease.

Researchers are investigating several ways to do this, including:

Gene therapy has some potential risks. A gene can't easily be inserted directly into your cells. Rather, it usually has to be delivered using a carrier, called a vector.

The most common gene therapy vectors are viruses because they can recognize certain cells and carry genetic material into the cells' genes. Researchers remove the original disease-causing genes from the viruses, replacing them with the genes needed to stop disease.

This technique presents the following risks:

The gene therapy clinical trials underway in the U.S. are closely monitored by the Food and Drug Administration and the National Institutes of Health to ensure that patient safety issues are a top priority during research.

Currently, the only way for you to receive gene therapy is to participate in a clinical trial. Clinical trials are research studies that help doctors determine whether a gene therapy approach is safe for people. They also help doctors understand the effects of gene therapy on the body.

Your specific procedure will depend on the disease you have and the type of gene therapy being used.

For example, in one type of gene therapy:

Viruses aren't the only vectors that can be used to carry altered genes into your body's cells. Other vectors being studied in clinical trials include:

The possibilities of gene therapy hold much promise. Clinical trials of gene therapy in people have shown some success in treating certain diseases, such as:

But several significant barriers stand in the way of gene therapy becoming a reliable form of treatment, including:

Gene therapy continues to be a very important and active area of research aimed at developing new, effective treatments for a variety of diseases.

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease.

Dec. 29, 2017

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Gene therapy - Mayo Clinic

Center for Gene Therapy :: The Research Institute at Nationwide …

The mission of the Center for Gene Therapy is to investigate and employ the use of gene and cell based therapeutics for prevention and treatment of human diseases including: neuromuscular and neurodegenerative diseases, lysosomal storage disorders, ischemia and re-perfusion injury, neonatal hypertension, cancer and infectious diseases.

Learn about our areas of focus and featured research projects.

The Center for Gene Therapy and the Viral Vector Core are home to a Good Manufacturing Practice (GMP) production facility for manufacture of clinical-grade rAAV vectors.

View the Viral Vector Core & Clinical Manufacturing Facility site.

TheOSU and Nationwide Children's Muscle Groupbrings together investigators with diverse research interests in skeletal muscle, cardiac muscle, and neuromuscular biology.

Hosted by Kevin Flanigan, MD,"This Month in Muscular Dystrophy" podcastshighlight the latest in muscular dystrophy and other inherited neuromuscular disease research.During each podcast, authors of recent publications discuss how their work improves our understanding of inherited neuromuscular diseases, and what their work might mean for treatment of these diseases.

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Center for Gene Therapy :: The Research Institute at Nationwide ...

Human Gene Therapy | Mary Ann Liebert, Inc. publishers

Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases.

The Journal is divided into three parts. Human Gene Therapy, the flagship, is published 12 times per year. HGT Methods, a bimonthly journal, focuses on the applications of gene therapy to product testing and development. HGT Clinical Development, a quarterly journal, serves as a venue for publishing data relevant to the regulatory review and commercial development of cell and gene therapy products.

Human Gene Therapy was voted one of the most influential journals in Biology and Medicine over the last 100 years by the Biomedical & Life Sciences Division of the Special Libraries Association.

Human Gene Therapy, HGT Methods, and HGT Clinical Development are under the editorial leadership of Editor-in-Chief Terence R. Flotte, MD, University of Massachusetts Medical School; Deput Editors Europe Nathalie Cartier, MD, INSERM, andThierry VandenDriessche, PhD, Free University of Brussels (VUB); Deputy Editors U.S. Barry J. Byrne, MD, PhD,Powell Gene Therapy Center, University of Florida, College of Medicine and Mark A. Kay, MD, PhD, Stanford University School of Medicine; Human Gene Therapy Editor Guangping Gao, PhD, University of Massachusetts Medical School; Methods Editor Hildegard Bning, PhD, Hannover Medical School; Clinical Development Editor James M. Wilson, MD, PhD,University of Pennsylvania School of Medicine, Gene Therapy Program; and other leading investigators. View the entire editorial board.

Audience: Geneticists, medical geneticists, molecular biologists, virologists, experimental researchers, and experimental medicine specialists, among others.

Human Gene Therapy and HGT Methods provide Instant Online publication 72 hours after acceptance

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Human Gene Therapy | Mary Ann Liebert, Inc. publishers

Foundation Fighting Blindness Celebrates Historic FDA …

Foundations early investment in LUXTURNA boosts vision-restoring treatment for people with RPE65 mutations and will help advance other gene therapies currently in development.

(Columbia, MD) Todays U.S. Food and Drug Administration (FDA) approval of voretigene neparvovec, to be marketed as LUXTURNA, will be life-changing for patients with vision loss due to mutations in the RPE65 gene and a watershed moment for the inherited retinal disease field, says the Foundation Fighting Blindness. The Foundation was an important early investor in LUXTURNA, providing $10 million in critical seed funding for the therapy.

The groundbreaking treatment is the first gene therapy for the eye and for any inherited disease to be approved by the FDA. The treatment restores vision by delivering working copies of the RPE65 gene directly into the retina, thereby compensating for the nonfunctional, mutated genes.

We are thrilled for the patients whose lives will change dramatically because of this treatment, says David Brint, Foundation Fighting Blindness chairman. We are also pleased to have this concrete example of the strength of the Foundations strategy of identifying and investing early in promising treatments. Doing so helps attract industry investment that can usher promising treatments through clinical trials and ultimately FDA approval.

LUXTURNA is the result of more than two decades of research and development at the University of Florida, the University of Pennsylvania, Childrens Hospital of Philadelphia, and Spark Therapeutics. The Foundation Fighting Blindness seed investment allowed researchers to take the therapy through the early investigational stages critical to any treatment development.

LUXTURNA will be life-changing for people with an inherited retinal disease caused by RPE65 mutations. For them, the treatment means a life of independence. Also important is the momentum this approval provides to other gene-based therapies for the eye and other diseases now in the clinic, says Benjamin Yerxa, PhD, Foundation CEO.

Twenty-four-year-old Katelyn Corey participated in the clinical trial that led to LUXTURNAs FDA approval. Before the trial, failing vision was causing her to consider giving up her lifelong dream of completing college and working in science. But, in December 2013, she received the RPE65 gene therapy in Sparks Phase 3 clinical trial, and her education and science career got quickly back on track.

Within days, I could see vibrant colors. I could even see the Philadelphia City Hall clock tower at night, she says. Also, now, I can go to a restaurant and see everything by candlelight, and I can see stars in the night sky. Corey recently earned a masters degree in epidemiology and now works as a research analyst for the U.S. Department of Veterans Affairs.

An additional noteworthy milestone is the demonstrated value of a new clinical endpoint devised by the Spark Therapeutics team to measure LUXTURNAs impact. The new measure, a multi-luminance mobility test (informally called the maze), measured the impact of the treatment beyond the traditional visual acuity measure the eye chart. This new clinical endpoint moves vision measures beyond the eye chart, which is particularly significant for people with low or no vision.

Spark Therapeutics, which holds the biologics license for LUXTURNA and conducted the clinical trials that showed its safety and efficacy, will also manage the treatment rollout. Spark has announced that in order to ensure the treatment is safely administered, it will only be available through a small number of centers of clinical excellence across the country. Spark has also expressed its commitment to educating third-party payers about the value of LUXTURNA and to working to help ensure treatment access to all eligible patients.

Anyone in need of more information about LUXTURNA should contact Spark Therapeutics at 1-833-SPARK-PS (833-772-7577). Another resource for information is Sparks website: http://www.Sparktx.com.

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The Foundation Fighting Blindness is the worlds leading private funder of research on potential treatments and cures for inherited retinal degenerative diseases and currently funds 77 research projects overseen by 65 investigators at 67 universities, hospitals, and affiliated eye institutes worldwide. The Foundation was established in 1971 and has since raised more than $725 million toward its mission to prevent, treat, and cure blindness caused by inherited retinal diseases. In excess of 10 million Americans, and millions more worldwide, experience vision loss due to retinal degenerations. Through its support of focused and innovative science, the Foundation drives the research that has and will continue to provide treatments and cures for people affected by retinitis pigmentosa, LCA, macular degeneration, Usher syndrome, and other retinal diseases.

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Gene Therapy Clinical Trials Databases

Wiley database on Gene Therapy Trials WorldwideThe Journal of Gene Medicine clinical trial site presenting charts and tables showing the number of approved, ongoing or completed clinical trials worldwide. Data is available for: Continents and countries where trials are being performed; Indications addressed; Vectors used; Gene types transferred; Phases of clinical trials; Number of trial approved/initiated 1989-2007.A searchable database is also present with detailed information on individual trials. The data are compiled and are regularly updated from official agency sources (RAC, GTAC etc..), the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. Beware that information on some trials is incomplete as some countries regulatory agencies simply do not disclose any information.See also: Gene therapy clinical trials worldwide to 2012 - an update. J. Gene Med. 2013 Feb;15(2):65-77.ClinicalTrials.gov database on clinical trials performed in the US and worldwideThe U.S. National Institutes of Health, through its National Library of Medicine, has developed ClinicalTrials.gov to provide patients, family members and members of the public current information about clinical research studies. The database is a registry of federally and privately supported clinical trials conducted in the United States and around the world. ClinicalTrials.gov gives you information about a trial's purpose, who may participate, locations, and phone numbers for more details.>> Overview of gene therapy trials recently received in the last 30 days. International Standard Randomised Controlled Trial Number RegisterThe ISRCTN Register is a register containing a basic set of data items on clinical trials that have been assigned an ISRCTN. Records are never removed from the ISRCTN Register (except in cases of duplications), which ensures that basic information about trials registered with an ISRCTN will always be available. The ISRCTN Register complies with requirements set out by the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the International Committee of Medical Journal Editors (ICMJE) guidelines, and complies with the WHO 20-item Trial Registration Data Set. Selected Gene Transfer and Therapy References databaseThe database is managed by Clinigene. The aim of this webpage is to provide database of selected references in the field of Gene Transfer and Therapy, addressing technological issues, applications, ethics and regulation from four main databases: Quality/Efficacy; Safety (pre-clinical); Adverse events (clinical); Important clinical trials. The database is open to the public and it is by no means intended to be either complete or comprehensive. Published Human Gene Therapy Clinical Trials database The database is maintained by Clinigene. The aim of this website is to provide a complete database of all published clinical gene therapy trials carried out worldwide. At this point in time the database is nearing completion and is open to the public.

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Gene Therapy Clinical Trials Databases

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