Archive for the ‘Gene Therapy Research’ Category

Gene therapy, also called gene transfer therapy, introduction of a normal gene into an individuals genome in order to repair a mutation that causes a genetic disease. When a normal gene is inserted into the nucleus of a mutant cell, the gene most likely will integrate into a chromosomal site different from the defective allele; although that may repair the mutation, a new mutation may result if the normal gene integrates into another functional gene. If the normal gene replaces the mutant allele, there is a chance that the transformed cells will proliferate and produce enough normal gene product for the entire body to be restored to the undiseased phenotype.

Human gene therapy has been attempted on somatic (body) cells for diseases such as cystic fibrosis, adenosine deaminase deficiency, familial hypercholesterolemia, cancer, and severe combined immunodeficiency (SCID) syndrome. Somatic cells cured by gene therapy may reverse the symptoms of disease in the treated individual, but the modification is not passed on to the next generation. Germline gene therapy aims to place corrected cells inside the germ line (e.g., cells of the ovary or testis). If that is achieved, those cells will undergo meiosis and provide a normal gametic contribution to the next generation. Germline gene therapy has been achieved experimentally in animals but not in humans.

Scientists have also explored the possibility of combining gene therapy with stem cell therapy. In a preliminary test of that approach, scientists collected skin cells from a patient with alpha-1 antitrypsin deficiency (an inherited disorder associated with certain types of lung and liver disease), reprogrammed the cells into stem cells, corrected the causative gene mutation, and then stimulated the cells to mature into liver cells. The reprogrammed, genetically corrected cells functioned normally.

Prerequisites for gene therapy include finding the best delivery system (often a virus, typically referred to as a viral vector) for the gene, demonstrating that the transferred gene can express itself in the host cell, and establishing that the procedure is safe. Few clinical trials of gene therapy in humans have satisfied all those conditions, often because the delivery system fails to reach cells or the genes are not expressed by cells. Improved gene therapy systems are being developed by using nanotechnology. A promising application of that research involves packaging genes into nanoparticles that are targeted to cancer cells, thereby killing cancer cells specifically and leaving healthy cells unharmed.

Some aspects of gene therapy, including genetic manipulation and selection, research on embryonic tissue, and experimentation on human subjects, have aroused ethical controversy and safety concerns. Some objections to gene therapy are based on the view that humans should not play God and interfere in the natural order. On the other hand, others have argued that genetic engineering may be justified where it is consistent with the purposes of God as creator. Some critics are particularly concerned about the safety of germline gene therapy, because any harm caused by such treatment could be passed to successive generations. Benefits, however, would also be passed on indefinitely. There also has been concern that the use of somatic gene therapy may affect germ cells.

Although the successful use of somatic gene therapy has been reported, clinical trials have revealed risks. In 1999 American teenager Jesse Gelsinger died after having taken part in a gene therapy trial. In 2000 researchers in France announced that they had successfully used gene therapy to treat infants who suffered from X-linked SCID (XSCID; an inherited disorder that affects males). The researchers treated 11 patients, two of whom later developed a leukemia-like illness. Those outcomes highlight the difficulties foreseen in the use of viral vectors in somatic gene therapy. Although the viruses that are used as vectors are disabled so that they cannot replicate, patients may suffer an immune response.

Another concern associated with gene therapy is that it represents a form of eugenics, which aims to improve future generations through the selection of desired traits. Some have argued that gene therapy is eugenic but that it is a treatment that can be adopted to avoid disability. To others, such a view of gene therapy legitimates the so-called medical model of disability (in which disability is seen as an individual problem to be fixed with medicine) and raises peoples hopes for new treatments that may never materialize.

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Gene therapy | medicine | Britannica.com

Gene therapy: The power of persistence

Nearly 50 years after the concept was first proposed, gene therapy is now considered a promising treatment option for several human diseases. The path to success has been long and tortuous. Serious adverse effects were encountered in early clinical studies, but this fueled basic research that led to safer and more efficient gene transfer vectors. Gene therapy in various forms has produced clinical benefits in patients with blindness, neuromuscular disease, hemophilia, immunodeficiencies, and cancer. Dunbar et al. review the pioneering work that led the gene therapy field to its current state, describe gene-editing technologies that are expected to play a major role in the field's future, and discuss practical challenges in getting these therapies to patients who need them.

Science, this issue p. eaan4672

Nearly five decades ago, visionary scientists hypothesized that genetic modification by exogenous DNA might be an effective treatment for inherited human diseases. This gene therapy strategy offered the theoretical advantage that a durable and possibly curative clinical benefit would be achieved by a single treatment. Although the journey from concept to clinical application has been long and tortuous, gene therapy is now bringing new treatment options to multiple fields of medicine. We review critical discoveries leading to the development of successful gene therapies, focusing on direct in vivo administration of viral vectors, adoptive transfer of genetically engineered T cells or hematopoietic stem cells, and emerging genome editing technologies.

The development of gene delivery vectors such as replication-defective retro viruses and adeno-associated virus (AAV), coupled with encouraging results in preclinical disease models, led to the initiation of clinical trials in the early 1990s. Unfortunately, these early trials exposed serious therapy-related toxicities, including inflammatory responses to the vectors and malignancies caused by vector-mediated insertional activation of proto-oncogenes. These setbacks fueled more basic research in virology, immunology, cell biology, model development, and target disease, which ultimately led to successful clinical translation of gene therapies in the 2000s. Lentiviral vectors improved efficiency of gene transfer to nondividing cells. In early-phase clinical trials, these safer and more efficient vectors were used for transduction of autologous hematopoietic stem cells, leading to clinical benefit in patients with immunodeficiencies, hemoglobinopathies, and metabolic and storage disorders. T cells engineered to express CD19-specific chimeric antigen receptors were shown to have potent antitumor activity in patients with lymphoid malignancies. In vivo delivery of therapeutic AAV vectors to the retina, liver, and nervous system resulted in clinical improvement in patients with congenital blindness, hemophilia B, and spinal muscular atrophy, respectively. In the United States, Food and Drug Administration (FDA) approvals of the first gene therapy products occurred in 2017, including chimeric antigen receptor (CAR)T cells to treat B cell malignancies and AAV vectors for in vivo treatment of congenital blindness. Promising clinical trial results in neuromuscular diseases and hemophilia will likely result in additional approvals in the near future.

In recent years, genome editing technologies have been developed that are based on engineered or bacterial nucleases. In contrast to viral vectors, which can mediate only gene addition, genome editing approaches offer a precise scalpel for gene addition, gene ablation, and gene correction. Genome editing can be performed on cells ex vivo or the editing machinery can be delivered in vivo to effect in situ genome editing. Translation of these technologies to patient care is in its infancy in comparison to viral gene addition therapies, but multiple clinical genome editing trials are expected to open over the next decade.

Building on decades of scientific, clinical, and manufacturing advances, gene therapies have begun to improve the lives of patients with cancer and a variety of inherited genetic diseases. Partnerships with biotechnology and pharmaceutical companies with expertise in manufacturing and scale-up will be required for these therapies to have a broad impact on human disease. Many challenges remain, including understanding and preventing genotoxicity from integrating vectors or off-target genome editing, improving gene transfer or editing efficiency to levels necessary for treatment of many target diseases, preventing immune responses that limit in vivo administration of vectors or genome editing complexes, and overcoming manufacturing and regulatory hurdles. Importantly, a societal consensus must be reached on the ethics of germline genome editing in light of rapid scientific advances that have made this a real, rather than hypothetical, issue. Finally, payers and gene therapy clinicians and companies will need to work together to design and test new payment models to facilitate delivery of expensive but potentially curative therapies to patients in need. The ability of gene therapies to provide durable benefits to human health, exemplified by the scientific advances and clinical successes over the past several years, justifies continued optimism and increasing efforts toward making these therapies part of our standard treatment armamentarium for human disease.

AAV and lentiviral vectors are the basis of several recently approved gene therapies. Gene editing technologies are in their translational and clinical infancy but are expected to play an increasing role in the field.

After almost 30 years of promise tempered by setbacks, gene therapies are rapidly becoming a critical component of the therapeutic armamentarium for a variety of inherited and acquired human diseases. Gene therapies for inherited immune disorders, hemophilia, eye and neurodegenerative disorders, and lymphoid cancers recently progressed to approved drug status in the United States and Europe, or are anticipated to receive approval in the near future. In this Review, we discuss milestones in the development of gene therapies, focusing on direct in vivo administration of viral vectors and adoptive transfer of genetically engineered T cells or hematopoietic stem cells. We also discuss emerging genome editing technologies that should further advance the scope and efficacy of gene therapy approaches.

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Gene therapy comes of age | Science

Media Advisory

Friday, January 12, 2018

No longer the future of medicine, gene therapy is part of present-day clinical treatment.

After three decades of hopes tempered by setbacks, gene therapythe process of treating a disease by modifying a persons DNAis no longer the future of medicine, but is part of the present-day clinical treatment toolkit. The Jan. 12 issue of the journal Science provides an in-depth and timely review of the key developments that have led to several successful gene therapy treatments for patients with serious medical conditions.

Co-authored by Cynthia E. Dunbar, M.D., senior investigator at the Hematology Branch of the National Heart, Lung and Blood Institute (NHLBI), part of the National Institutes of Health, the article also discusses emerging genome editing technologies. According to Dunbar and her colleagues, these methods, including the CRISPR/Cas9 approach, would provide ways to correct or alter an individual's genome with precision, which should translate into broader and more effective gene therapy approaches.

Gene therapy is designed to introduce genetic material into cells to compensate for or correct abnormal genes. If a mutated gene causes damage to or spurs the disappearance of a necessary protein, for example, gene therapy may be able to introduce a normal copy of the gene to restore the function of that protein.

The authors focused on the approaches that have delivered the best outcomes in gene therapy so far: 1) direct in vivo administration of viral vectors, or the use of viruses to deliver the therapeutic genes into human cells; and 2) the transfer of genetically engineered blood or bone marrow stem cells from a patient, modified in a lab, then injected back into the same patient.

Originally envisioned as a treatment solely for inherited disorders, gene therapy is now being applied to acquired conditions such as cancer. For example, the engineering of lymphocytes, white blood cells, that can be used in the targeted killing of cancer cells.

In 2017, a steady stream of encouraging clinical results showed progress in gene therapies for hemophilia, sickle-cell disease, blindness, several serious inherited neurodegenerative disorders, an array of other genetic diseases, and multiple cancers of the bone marrow and lymph nodes.

Three gene therapies have been approved by the U.S. Food and Drug Administration in the past year, and many more are under active clinical investigation. The authors looked to the future of gene therapies, and the challenges of delivering these complex treatments to patients.

Much of this research has been funded by NIH, and key advances took place in the NIH Clinical Center.

Cynthia E. Dunbar, M.D., senior investigator, Hematology Branch, NHLBI, NIH, is available for comments.

Dunbar et al., Gene therapy comes of age. Science 359, eaan4672 (2018)

For more information or to schedule an interview, please contact the NHLBI Office of Science Policy, Engagement, Education, and Communications at 301-496-5449 or nhlbi_news@nhlbi.nih.gov.

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at https://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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The coming of age of gene therapy: A review of the past ...

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.

Sept. 13, 2016

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Gene therapy - About - Mayo Clinic

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Rett Syndrome, as awful as the symptoms may be, provides us with several enormous advantages. First we know the cause: mutations in a single gene: MECP2. Second, Rett is not degenerative brain cells dont die. Third, work from RSRT trustee, Adrian Bird, suggests that the symptoms of Rett need not be permanent. These three facts make gene therapy an attractive therapeutic strategy.

In 2014 we launched a bold international collaboration of two gene therapy labs, Brian Kaspar and Steven Gray, and two MECP2 labs, Gail Mandel and Stuart Cobb. Together these labs brought together all the necessary skills and experience to determine if gene therapy is a viable therapeutic.

The Consortium worked through numerous challenges involving vector optimization (the Trojan horse that delivers the gene into a cell), gene construct optimization (what you package into the vector that regulates MeCP2 protein production), gene therapy dosage, and the best route to deliver it.

The data generated by the Consortium exceeded our expectations. They were able to develop a gene therapy product candidate with impressive efficacy, safety and delivery characteristics. Importantly, the magnitude of improvement in the mouse models of Rett is much greater than that of any drug tested and suggests that significant benefit may be achieved in people. We expect improvements, at least to some degree, regardless of age.

Based on the Consortium data the biotech company, AveXis, has now committed to advancing a gene therapy candidate into clinical trials. The company will announce before the end of 2017 what their timeline for trials will be.

Technological advances in gene therapy are happening quickly with more effective vectors being discovered that can carry larger DNA cargos and target a greater percentage of brain cells. While we anticipate encouraging results with our first clinical trial there will undoubtedly be room to improve. We have therefore recently awarded continued funding to the Gene Therapy Consortium to support second-generation gene therapy programs to leverage all technological advances.

Targeting the root problem in Rett, MECP2, can be done either at the DNA level (gene therapy or MECP2 Reactivation), the mRNA level or protein level.

Both the DNA and protein approaches carry a risk of potential dosage problems (too much MeCP2 may be harmful). An alternative approach is to use a technology called Spliceosome-Mediated RNA Trans-Splicing (SMaRT). This technology allows a mutation to be spliced out and repaired in RNA. The advantage is that this approach avoids any potential over-expression issues. Consortium member, Stuart Cobb, is working on this approach.

Gail Mandel of the Consortium is working on yet another approach, RNA editing. The possibility of correcting mutations in RNA has profound therapeutic potential, but had remained largely theoretical. Our focused investments have already demonstrated the potential for correcting MECP2 mutations in RNA in cells. We are currently increasing our investment to improve the editing efficiency and to identify optimal delivery methods.

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Gene Therapy Consortium - Rett Syndrome Research Trust

Germline Gene Transfer

Gene transfer represents a relatively new possibility for the treatment of rare genetic disorders and common multifactorial diseases by changing the expression of a person's genes. Typically gene transfer involves using a vector such as a virus to deliver a therapeutic gene to the appropriate target cells. The technique, which is still in its infancy and is not yet available outside clinical trials, was originally envisaged as a treatment of monogenic disorders, but the majority of trials now involve the treatment of cancer, infectious diseases and vascular disease. Human gene transfer raises several important ethical issues, in particular the potential use of genetic therapies for genetic enhancement and the potential impact of germline gene transfer on future generations.

Gene transfer can be targeted to somatic (body) or germ (egg and sperm) cells. In somatic gene transfer the recipient's genome is changed, but the change is not passed on to the next generation. In germline gene transfer, the parents' egg and sperm cells are changed with the goal of passing on the changes to their offspring. Germline gene transfer is not being actively investigated, at least in larger animals and humans, although a great deal of discussion is being conducted about its value and desirability.

Many people falsely assume that germline gene transfer is already routine. For example, news reports of parents selecting a genetically tested egg for implantation or choosing the sex of their unborn child may lead the public to think that gene transfer is occurring, when actually, in these cases, genetic information is being used for selection, with no cells being altered or changed. In addition, in 2001 scientists confirmed the birth of 30 genetically altered children whose mothers had undergone a procedure called ooplasmic transfer. In this process, doctors injected some of the contents of a healthy donor egg into an egg from a woman with infertility problems. The result was an egg with two types of mitochondria, cellular structures that contain a minuscule amount of DNA and that provide energy for the cell. The children born following this procedure thus have three genetic parents, since they carry DNA from the donor as well as the mother and father. Although the researchers announced this as the "first case of human germline genetic modification," the gene transfer was an inadvertent side effect of the infertility procedure.

Many factors have prevented researchers from developing successful gene transfer techniques in both somatic and germline attempts (the latter in animals). The first hurdle is the gene delivery tool. The new gene is inserted into the body through vehicles called vectors (gene carriers), which deliver therapeutic genes to the patients' cells. Currently, the most common vectors are viruses, which have evolved a mechanism to encapsulate and deliver their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of the virus's biology and manipulate its genome to remove human disease-causing genes and insert therapeutic genes. However, viruses, while effective, introduce other problems to the body, such as toxicity, immune and inflammatory responses, and gene control and targeting issues. Complexes of DNA with lipids and proteins provide an alternative to viruses, and researchers are also experimenting with introducing a 47th (artificial human) chromosome to the body that would exist autonomously along side the standard 46 chromosomes, presumably not affecting their functioning or causing any mutations. An additional chromosome would be a large vector capable of carrying substantial amounts of genetic code, and it is anticipated that, because of its construction and autonomy, the body's immune systems would not attack it.

Some of the concerns raised about somatic gene transfer are related to the possibility that it could inadvertently lead to germline gene transfer. The possibility of germline modification through these techniques is the result of the hit-or-miss nature of the current technologies. It is always possible that a vector will introduce the gene into a cell other than that for which it is supposed to be targeted (e.g., a spermatocytic cell) or that through a secondary mechanism target cells that have taken up the new gene will through some independent natural process (such as transfection) transfer the gene to a germline cell. Moreover, if somatic gene transfer were to be conducted in utero, especially before the second trimester, it would increase the likelihood that some of the cells into which the gene is taken up will become part of the germline. It is possible that to effectively treat certain diseases using gene transfer, it might be necessary to apply somatic techniques early in development so that germline transfer is inevitable.

In contrast to inadvertent germline transfer following somatic gene transfer, intentional germline gene transfer would involve the deliberate introduction of new genetic material into either germ cells (sperm or oocytes) or into zygotes in vitro prior to fertilization or implantation. Currently, this technology has not been applied to humans; however, it has been successfully applied to some plants and animals. The aim of this process is to produce a developing embryo in which each cell (including those that will develop into gametes in the future) carries the newly inserted gene as part of its genetic make-up.

Current efforts in animals have demonstrated the difficulty of this approach. Some cells do not acquire the gene or acquire multiple or partial copies of the gene. In addition, it is not yet possible to specify with any accuracy where in the genome the new gene will be introduced, and some insertion locations may interfere with other important genes. If these kinds of errors are detected, then theoretically embryos with these defects could be "selected out." However, should germline gene transfer be attempted in humans, it is likely that not all errors introduced as a result of the gene transfer will be detected.

Currently, however, animal studies have shown that gene transfer approaches that involve the early embryo can be far more effective than somatic cell gene therapy methodologies used later in development, depending on the complexity of the trait that is being improved or eliminated. Embryo gene transfer affords the opportunity to transform most or all cells of the organism and thus overcome the inefficient transformation that plagues somatic cell gene transfer protocols. Gene transfer selects one relevant locus for a trait (when in fact there might be many interactive loci) and then attempts to improve the trait in isolation. This approach, while potentially more powerful and efficient than conventional breeding techniques, involves more uncertainty risks.

Thus, both kinds of studies - germline gene transfer at the gamete and zygote stages - have significant risks. In cases in which the gene has failed to be introduced or fails to be activated, the resulting child would likely be no worse off than he or she would have been without the attempted gene transfer. However, those with partial or multiple copies of a gene could be in significantly worse condition. The problems resulting from errors caused by the gene insertion could be severe - even lethal - or they might not be evident until well after the child has been born, perhaps even well into adulthood, when the errors could be passed on to future generations. For these reasons, given the limits of current technology, germline gene transfer has been considered ethically impermissible.

Beyond the medical risks to the potential child, a number of long-standing ethical concerns exist regarding the possible practice of germline gene transfer in both human and nonhuman cases. Such modifications in human beings raise the possibility that we are changing not merely a single individual but a host of future individuals as well, with potential for harm to occur to those individuals and perhaps to humanity as a whole. Concerns involve issues ranging from the autonomy of future individuals to distributive justice, fairness, and the application of these technologies to "enhancement" rather than treating disease. In germline gene transfer, the persons being affected by the procedure - those for whom the procedure is undertaken - do not yet exist. Thus, the potential beneficiaries are not in a position to consent to or refuse such a procedure.

Gene transfer clinical trials have a unique oversight process that is conducted by the National Institutes of Health (NIH) through the Recombinant DNA Advisory Committee (RAC) and the NIH Guidelines for Research Involving Recombinant DNA Molecules, and by the Food and Drug Administration (FDA) through regulation (including scientific review, regulatory research, testing, and compliance activities, including inspection and education). Of note, FDA regulations apply to all clinical gene transfer research, while NIH governs gene transfer research that is supported with NIH funds or that is conducted at or sponsored by institutions that receive funding for recombinant DNA research. Currently, the majority of somatic cell gene transfer research is subject to the NIH Guidelines; however RAC will not currently consider protocols using germline gene transfer.

In addition, NIH has added to its guidelines the following statement:

The RAC continues to explore the issues raised by the potential of in utero gene transfer clinical research. However, the RAC concludes that, at present, it is premature to undertake any in utero gene transfer clinical trial. Significant additional preclinical and clinical studies addressing vector transduction efficacy, biodistribution, and toxicity are required before a human in utero gene transfer protocol can proceed. In addition, a more thorough understanding of the development of human organ systems, such as the immune and nervous systems, is needed to better define the potential efficacy and risks of human in utero gene transfer. Prerequisites for considering any specific human in utero gene transfer procedure include an understanding of the pathophysiology of the candidate disease and a demonstrable advantage to the in utero approach. Once the above criteria are met, the RAC would be willing to consider well rationalized human in utero gene transfer clinical trials.

Prepared by Kathi E. Hanna, M.S., Ph.D., Science and Health Policy Consultant

Last Reviewed: March 2006

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Germline Gene Transfer - National Human Genome Research ...

Interest in the field of genome editing continues to heat up, fueled by technological advances and the first approval of a gene therapy in the United States. The latest development in this exciting frontier of science involves small viruses called AAVs (short for adeno-associated viruses) that have the power to overwrite DNA in human cells.

AAV biology is one of the most febrile areas of basic research, and were planning to explore its therapeutic potential through a new collaboration, says Craig Mickanin, who focuses on new tools and technologies as a director at the Novartis Institutes for BioMedical Research (NIBR).

Novartis will work with Homology Medicines, a biotech company with a proprietary AAV platform, to adapt and refine the technology for the treatment of a blood disorder and certain eye diseases. Novartis biologists with expertise in these conditions will work side-by-side with Homology scientists over the course of the collaboration announced November 13 to move projects toward clinical testing.

The collaboration is designed to accelerate an initiative at NIBR that engages researchers across the company who are involved in projects with a common denominator: the genetic reprogramming of cells. Homologys AAV technology may aid their work.

It is our hope that this collaboration will help advance our Cell and Gene Therapy initiative, says Susan Stevenson, an executive director at NIBR who leads the initiative.

AAV biology is one of the most febrile areas of basic research, and were planning to explore its therapeutic potential through a new collaboration.

Craig Mickanin, a director at NIBR who focuses on new tools and technologies

AAVs are unusual in one key respect. In contrast to larger viruses, they dont seem to cause illness. This built-in safety feature makes AAVs attractive tools for genome editing.

The benign viruses can be engineered to carry a specific genetic sequence, and they can be programmed to home in on a target site in the genome. When they arrive, AAVs trigger a process called homologous recombination, which overwrites a particular portion of a gene or even replaces an entire gene. In this way, AAVs can be used to correct genetic defects.

Homologous recombination may give AAVs an edge over other genome editing tools such as CRISPR in certain contexts.

Unlike AAVs, CRISPR employs molecular scissors to generate double-stranded breaks in DNA. The breaks can be repaired one of two ways. The repair mechanism that tends to dominate called non-homologous end joining results in the insertion or deletion of short DNA sequences, which typically break the original gene. As a result, its relatively easy for researchers to disrupt a gene with CRISPR, but its harder for them to fix an error in a gene.

We aim to select the right tool for the right project, says Mickanin, the technology specialist. In some cases, that will mean using AAVs to correct a genetic defect rather than disabling a gene.

The collaboration with Homology includes three work streams. The first focuses on a blood disorder. The Novartis-Homology team hopes to design a single AAV reagent that can be injected directly into the bloodstream of any patient with a defective gene to cure the disease. We want to figure out if these AAVs are safe enough to inject directly into the bloodstream and if we can use them to fix a defective gene once and for all, says Stevenson, the cell and gene therapy expert.

The second work stream involves diseases of the eye, a testing ground for gene editing therapies because such therapies can be delivered locally. Gene editing agents can be injected directly under the retina, for example, where researchers hope they will work without affecting the rest of the body. The fact that we can directly observe the treatment and its effects in the eye gives us an important opportunity for assessing gene editing efficacy and helping patients with eye disease, explains Cynthia Grosskreutz, Global Head of Ophthalmology at NIBR.

The final work stream is exploratory. Researchers from across NIBR will be able to nominate projects that could benefit from Homologys AAV technology. Homologys viruses will be tested on a variety of cell types and model systems, potentially exposing new opportunities for therapeutic applications.

This technology could be applied to many different diseases, Mickanin says. Were excited to work with the Homology team to explore the possibilities.

In addition to collaborating with Homology Medicines, Novartis has made an equity investment in the company.

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Small viruses could accelerate cell and gene therapy research

Ongoing gene therapy trials open to enrollment

These studies are actively seeking new participants.

The purpose of this study is to learn about a new gene therapy that may help patients with Achromatopsia. This is the first study that aims to treat Achromatopsia disease by gene therapy. The study investigators want to find out whether it is safe for use in humans. The gene therapy is given by a surgical injection into the retina (the lining of the back of the eye that detects light) of one eye. The eye with worse vision will receive the gene therapy.

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The purpose of this study is to learn about a new gene therapy that may help patients with Achromatopsia. The study investigators want to find out whether it is safe for use in humans. The gene therapy is given by a surgical injection into the retina (the lining of the back of the eye that detects light) of one eye. The eye with worse vision will receive the gene therapy.

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The purpose of this study is to learn about a new gene therapy that may help patients with X-Linked Retinoschisis (XLRS).This is the first study that aims to treat XLRS disease by gene therapy. The study investigators want to find out whether it is safe for use in humans. The gene therapy is given by a surgical injection into the vitreous (a thick, gel-like transparent substance that fills the center of the eye) of one eye. The eye with worse vision will receive the gene therapy.

Contact 503 494-0020 or email the ORDC.

The purpose of this study is to learn about a new gene therapy being studied in patients with Retinitis Pigmentosa (RP) as a result of Usher Syndrome.This is the first study that aims to treat RP due to Usher Syndrome by gene therapy.The study investigators want to find out if UshStat is safe for use in humans.The gene therapy is given by surgical injection underneath the retina of one eye.The eye with worse vision will receive the gene therapy

Contact 503 494-0020 or email the ORDC.

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The purpose of this study is to learn about a new gene therapy that may help patients with Stargardt's Macular Degeneration (SMD). This is the first study that aims to treat Stargardt's disease by gene therapy. The study investigators want to find out whether it is safe for use in humans. The gene therapy is given by a surgical injection underneath the retina of one eye. The eye with worse vision will receive the gene therapy.

Contact 503 494-0020 or email the ORDC.

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Purpose: To evaluate the safety and dosing levels of a gene-based treatment, RetinoStat, for wet AMD. In this study, two helpful genes are delivered directly to the retina, where they "turn on" proteins that block abnormal blood vessel growth in a sustained fashion. Enrollment is completed and study patients are being followed.

Contact: Ann Lundquist, 503 494-6364.

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Gene therapy at OHSU Casey Eye Institute | Casey Eye ...

If your application is for ethical approval of a gene therapy clinical trial you must apply to the Gene Therapy Advisory Committee (GTAC).

GTAC is the UK national REC for gene therapy clinical research according to regulation 14(5) of The Medicines for Human Use (Clinical Trials) Regulations 2004.

You may book applications to the following RECs:

Once a booking is accepted, you must electronically submit your application and supporting documentation on the same day. If your application is valid, you will be sent an acknowledgement within five days of receipt and arrangements subsequently made for you to attend the REC meeting.

Historically, GTAC would send applications for external peer review. In future, as with all other RECs, the responsibility for providing peer review will rest with the sponsor.

We will seek to work in partnership with other organisations to determine whether it is possible to develop some agreed standards. More information can be found here.

You are no longer required to seek pre-application regulatory advice from GTAC. The MHRA will continue to provide this service to commercial companies, and will consider requests for advice from academic researchers.

Members of the research community have requested clarity on the type of application that needs to be submitted to GTAC.

Legally, all gene therapy applications must be submitted to a GTAC that is able to transfer to other designated RECs.

To make it easier for researchers and sponsors to identify other studies needing review, other applications that involve cell therapy and/or that are submitted to the MHRA Clinical Trials Expert Advisory Group must also be submitted to GTAC.

All gene therapy and cell therapy applications for Clinical Trials Authorisation will be assessed by the MHRA and, where appropriate will now be submitted to the MHRA Clinical Trials Expert Advisory Group for review. This review will assure the RECs that appropriate scrutiny of the safety of the application has been carried out.

The REC will raise any concerns directly with the MHRA.

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Gene Therapy Advisory Committee - Health Research Authority

Gene therapy is a type ofbiological therapy for cancer that is still in the early stages of research.

Genes are coded messages that tell cells how to make proteins. Proteins are the molecules that control the way cells behave. Our genes decide what we look like and how our body works.We have many thousands of separate genes.

Genes are made ofDNAand they are in the nucleus of the cell. The nucleus is the cell's control centre.Genes are grouped together to make chromosomes. We inherit half our chromosomes from our mother and half from our father.

Cancer cells are different from normal cells. They have changes (called faults or mutations) in several of their genes which make them divide too often and form a tumour. The genes that are damaged mightbe:

Many gene changes that may make a cell become cancerous are caused by environmental or lifestyle factors, such as smoking.

Some people have inherited faulty genes that increase their risk of particular types of cancer. Inherited damaged genes cause between 2 and 3 in every 100 (2% to 3%) of cancers.

Gene therapy is a type of treatment which uses genes to treat illnesses. Researchers have been developing differenttypes of gene therapyto treat cancer.

The ideas for these new treatments have come about because we are beginning to understand how cancer cells are different from normal cells. It is stillearly days for this type of treatment. Some of these treatments are being looked at in clinical trials. Otherscan now be used for some people with types of cancer such as melanoma skin cancer.

Getting genes into cancer cells is one of the most difficult aspects of gene therapy. Researchers are working on finding new and better ways of doing this. The gene is usually taken into the cancer cell by a carrier called a vector.

The most common types of carrier used in gene therapy are viruses because they can enter cells and deliver genetic material. The viruses have been changed so that they cannot cause serious disease but they may still cause mild, flu like symptoms.

Some viruses have been changed in the laboratory so that they target cancer cells and not healthy cells. So they only carry the gene into cancer cells.

Researchers are testing other types of carrier such as inactivated bacteria.

Researchers are looking at different ways of using gene therapy:

Some types of gene therapy aim to boost the body's natural ability to attack cancer cells. Ourimmune systemhas cells that recognise and kill harmful things that can cause disease, such as cancer cells.

There are many different types of immune cell. Some of them produce proteins that encourage other immune cells to destroy cancer cells. Some types of therapy add genes to a patient's immune cells. Thismakes them better at finding or destroying particular types of cancer.

There are a few trials using this type of gene therapy in the UK.

Some gene therapies put genes into cancer cells to make the cells more sensitive to particular treatments. The aim is to make treatments,such as chemotherapy or radiotherapy, work better.

Some types of gene therapy deliver genes into the cancer cells that allow the cells to change drugs from an inactive form to an active form. The inactive form of the drug is called a pro drug.

First of all you have treatment with the the carrier containing the gene, then you havethe pro drug.The pro drug circulates in the body and doesn't harm normal cells. But when it reaches the cancer cells, it is activated by the gene and the drug kills the cancer cells.

Some gene therapies block processes that cancer cells use to survive. For example, most cells in the body are programmed to die if their DNA is damaged beyond repair. This is called programmed cell death or apoptosis. Cancer cells block this process so they don't die even when they are supposed to.

Some gene therapy strategies aim to reverse this blockage. Doctors hope these new types of treatment will make the cancer cells die.

Some viruses infect and kill cells. Researchers are working on ways to change these viruses so they only target and kill cancer cells, leaving healthy cells alone.

This sort of treatment uses the viruses to kill cancer cells directly rather than to deliver genes. So it is not cancer gene therapy in the true sense of the word. But doctors sometimes refer to it as gene therapy.

A drug called T-VEC (talimogene laherparepvec)isnowavailable as a treatmentfor melanoma skin cancer. It isalso calledImlygic. It is also being looked at in trials for other types of cancer, such as head and neck cancer.

T-VEC uses a strain of the cold sore virus (herpes simplex virus)that been changed by altering the genes that tell the virus how to behave. It tells the virus to destroy the cancer cells and ignore the healthy cells.

T-VEC can beused to treatsome people with melanoma skin cancer whose cancer cannot be removed with surgery. You have T-VEC as an injectiondirectly into yourmelanoma.

Use the tabs along the top to look at recruiting,closed and results.

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Gene therapy | Cancer in general | Cancer Research UK

"The event reflected the fantastic growing enthusiasm around cell and gene therapy, including small and large companies, investors and regulators. It was great to see everyone so engaged and so positive. The event really gives you the pulse of what is happening right now in cell and gene therapy."

Vice President, Regulatory Science, Bluebird Bio, Inc

Great program, great people, great venue.

Managing Director, EUFETS GmbH

Dynamic, interesting and highly interactive event that promotes exchange and networking in highly specialized field of gene therapy.

Associate Director, Powell Gene Therapy Center, University of Florida

"Phacilitate provides a unique forum, bringing together research, process development, and commercial leaders on the cutting edge of cell, gene, and immunotherapy. A great conference for anyone wanting a comprehensive view of the field."

Vice President, Research & Product Development, Dendreon

"It was all business. Ive never been to an event where over 80% of the conversations I had were constructive to my business objectives."

Acquisition & Business Development Manager, BioMedical Materials, Chemelot Campus B.V.

Great way to expand network with global experts in cell and gene therapy who are facing similar challenges.

Director, Strategy and Engagement, GSK

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Home - Cell & Gene Therapy World 2018 - Meet the Future of ...

By

September 7, 2017, 2:04 PM EDT

A week after its landmark approval of the first treatment thatworks by genetically altering a patients cells, the U.S. health regulator vowed to modernize to keep up with the fast-moving field of biotechnology research.

We are at a point in the history of medicine that is similar to other great inflections in science where fundamental principles of science and medicine became firmly established as part of a leap in public health, Food and Drug Administration Commissioner Scott Gottlieb said in a speech in Washington. FDAs goal is to make sure that our policies are as scientifically advanced as the products were being asked to evaluate.

Gottllieb vowed to betteradjust to the complexities of novel therapies and make sure the agencys policies match the challenges faced by companies looking to follow in the footsteps of Novartis AG, whose Kymriah drug was just approved for pediatric patients with a hard-to-treat form of leukemia. The FDA is evaluating more than 550 applications to test gene therapies and 76 related to CAR-T, the same class of compounds as Kymriah, Gottlieb said in his address to Research America, a nonprofit public education and advocacy group dedicated to health and science research.

The speech could be good news for the developers of therapies using the patients own immune system to attack tumors, including Kite Pharma Inc., which is awaiting approval for a CAR-T treatment. FDAs faster-than-expected approval of Novartiss Kymriah sent biotech shares higher last week. That optimism was tempered this week when one drugmaker halted two studies of an experimental blood cancer therapy after a patient died -- a reminder of the major risks and safety concerns in the nascent field.

Gottlieb focused his talk on the earliest stage of drug development, before potential new compounds make it into patients. The agency will engage earlier with companies and researchers working in these new areas, including technology platforms like gene therapy, cell therapy and regenerative medicine, he said.

Some academic and industry drug developers arent fully aware of what is is needed to get a new product approved, particularly smaller groups that often are working with the most innovative technology, he said. Others overestimate the amount of information the agency needs to start studies in patients. FDA staff will work with researchers to eliminate unnecessary steps and incorporate new testing approaches that may help cut costs and speed the approval process, he said.

Information that is gleaned from early work in CRISPR, a technology that allows researchers to easily manipulate genes in a way that many hope will one day be used to treat disease, may be used to hasten development of other products, the commissioner said.

Read More: Groundbreaking cancer research -- a QuickTake on immunotherapy

In many cases, the main challenges of novel medicines arent clinical questions about how well they work and their immediate safety, but newer issues related to how they are produced and delivered to the patient, the commissioner said. Manufacturing CAR-Ts like Kymriah, for instance, involves extracting infection-fighting cells from the patients blood; sending them to a centralized plant in New Jersey to get re-programmed; and shipping them back to be re-infused into the patient at medical centers.

The new therapies may also carry long-term risks that may not materialize for years -- if ever. Attention will be needed on how the therapies hold up during routine use, with risks and benefits that are closely monitored for years, he said.

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FDA Vows Modernization to Keep Up With Biotech Advances - Bloomberg

For 23 years, North Branford's Caruso-Bode family has been pushing to find a cure for Friedreich's Ataxia (FA), even as the life-shortening, degenerative neuro-muscular disorder has continued to deepen its toll on the family's inspiring, courageous siblings, Sam and Alex Bode. On Friday, Sept. 22, family and friends hope the community will continue to support their efforts, by joining in on an annual night of fun, food and fundraising to help find a cure for FA.

This year's event has the theme"Living a Happy Life" and gets underway at 6 p.m. at Branford's Owenego Beach and Tennis Club. Tickets are $50 per person, withappetizers, dinner by Outback Steakhouse, acash bar, araffleand "...many unique participants to entertain guests throughout the evening," according to an event press release. The releasealso shared Alex Bode's sentiment thatthe community spirit, friendship, kindness and love experienced at the event each year,"...keeps Sam and I optimistic and really feeling supported."

The siblings were diagnosed with FA as children. Sam Bode was first diagnosed with FA in 1995; followed shortly by the same diagnosis in Alex.Throughthe years and in many ways, Sam, now 31, and Alex, now 27,have done much to help their mother, Mary Caruso, in raising awareness and funding for research as well as workingto promoteacceptance of differences.Caruso was also afounding member of nationalnon-profit Friedreich's Ataxia Research Alliance (FARA), which was started in September 1998 by a group of FA patient families and three of the world's leading FA scientists. Proceeds from the Sept. 22 event will help FARA continue to fund research.

In the last 20 years, research has progressed to the point that scientists are nowcloser than ever to the hope of finding a cure, said Caruso.Recent gains in gene therapy research, with clinical trials as the hoped-for nextstep,could bring aboutpositive, targeted results.One area of the work, cardiac gene therapy, will zero in on FA-related heart disease, which recently became an issue facing the Caruso/Bode family. The family is also hopeful about news of another promisingarea of research, which couldrestore eyesight loss due to FA.The Bode siblingsrecently lost their eyesight due to the progressive disease.

"These are the losses that really hit home," said Caruso. "Both Sam and Alex have recently had to stop riding their hand trikes outside, [the] one activity they both enjoyed so much. To watch them lose the few activities they enjoy is so difficult."

As always, the siblings are continuing to face FA with "such courage," said their mom. The devastating, progressiveeffects of the disorderare part of a daily battle usually witnessed by only those closest to the family. Becauseso many in thecommunity may not see the struggle, Caruso wonders if perhaps some may feel as if being asked to help her family find a cure for FA may be asking too much.

"I have found part of the loneliness of it is, when you have a progressive disease without a cure, I think people like to say, 'Holy Cow -- them again?' You get numb to it," said Caruso. "Unfortunately, that is our life. For us, it's an ongoing battle, and you have to always stay ahead of the game, and you have to stay optimistic. We'd love to say we have a treatment, or we have something to try; but we don't yet. That's the reality of it. But we have try."

Join the Caruso/Bode family for an evening of fun, food and fundraising to find a cure for Friedreich's Ataxia; 6 p.m. - 10p.m.Friday, Sept. 22, Owenego Beach and Tennis Club, 40 Linden Ave. Branford. Tickets, $50 available online hereor by calling (203) 246-8820 or (203) 889-6484. All proceeds assist research supported by FARA, a national, public, 501(c) (3) nonprofit, tax-exempt organization. See more information at http://www.curefa.org

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Closer Than Ever to a Cure: Annual FA Fundraiser Sept. 22 in Branford - Zip06.com

University of Minnesota groundbreaking gene therapy research

Lindsey Seavert, KARE 6:54 PM. CDT September 06, 2017

Andrea and RyanShaughnessy, from the Traverse City, Michigan area, have been at the University of Minnesota Masonic Childrens Hospital for nine months, as their son, Anderson, 2, underwent two blood stem cell transplants for Hurler Syndrome. (Photo: KARE 11)

MINNEAPOLIS - The FDA just recently approved the first gene therapy available in the United States for childhood leukemia, ushering in a new frontier in medicine to reprogram a patient's own cells to attack a deadly cancer.

The breakthrough is also bringing a long-awaited promise at the University of Minnesota for children undergoing treatment for rare, life-threatening diseases.

An estimated 20 families whose children have undergone blood stem cell transplants for rare metabolic diseases, have joined together to launch a crowdfunding campaign to help U of M doctors research safer, more effective therapies, including new gene therapy that could bring life-saving impact for their children.

Andrea and Ryan Shaughnessy, from the Traverse City, Michigan area, have been at the University of Minnesota Masonic Childrens Hospital for nine months, as their son, Anderson, 2, underwent two blood stem cell transplants for Hurler Syndrome.

The rare genetic disease, affecting 1 in every 100,000 children, occurs when the body has a defective gene and as a result, cannot make an important enzyme. Children with Hurlers Syndrome have a life expectancy of 5 to 10 years old.

Time is not on our side, the more we can do earlier on, the better off it is for his long-term survival and development, said Andrea Shaughnessy. If we could help keep anybody else from living in our shoes because it is so hard, you know it might not be able to directly impact the help Anderson needs today, but it doesnt mean that we cant help others so they can have a better outcome and life expectancy tomorrow.

The Shaughnessy family made the second donation to the crowdfunding campaign, called the Pediatric BMT Metabolic Program Research Fund.

I think its really inspiring they are doing this, said Dr. Weston Miller, a U of M pediatric blood and marrow physician overseeing many blood stem cell transplants. Research is expensive and really driving novel therapies and improving on existing therapies takes time and money.

Dr. Miller noted the lack of research and development for rare diseases, and said the gene therapy reduces the health risks associated with undergoing and surviving blood stem cell transplants.

Really the unifying theme of all these novel therapies is going to be make it safer and more effective, said Dr. Miller. So, what we of course wish and hope for is we can find a way to have effective therapies and look Mom and Dad in the eye, and say there is closer to 100 percent they will be walking out of here.

The families from across the country and world have a goal to raise $1 million to fund research projects that might otherwise never make it to the laboratory.

We are pretty proud of this team and we know they can do it, its amazing the tenacity they bring, said Andrea Shaughnessy.

The crowdfunding page details their plea for support.

They have helped countless families from all around the world navigate the uncertainty of a life-threatening diagnosis and make heart-wrenching decisions. They go above and beyond, whether it is Google translating an email to correspond with parents in other countries or wearing a Minions shirt. They have revolutionized the way the diseases are treated, drastically improved the quality of life for many of their patients, and given families hope.

2017 KARE-TV

Excerpt from:
Families raise money for research into rare diseases - KARE

DUBLIN--(BUSINESS WIRE)--The "Gene Therapy - Technologies, Markets and Companies" report from Jain PharmaBiotech has been added to Research and Markets' offering.

The markets for gene therapy are difficult to estimate as there is only one approved gene therapy product and it is marketed in China since 2004. Gene therapy markets are estimated for the years 2016-2026.

The estimates are based on epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright.The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

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 76 tables and 22 figures.

Profiles of 189 companies involved in developing gene therapy are presented along with 240 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold within a decade.

These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report. John Wiley & Sons published the book in 2000 and from 2001 to 2003, updated versions of these companies (approximately 160 at mid-2003) were available on Wiley's web site. Since that free service was discontinued and the rights reverted to the author, this report remains the only authorized continuously updated version on gene therapy companies.

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/q99xbz/gene_therapy

Excerpt from:
Global Updated Gene Therapy Technologies, Markets and Companies Report 2017-2026 - Research and Markets - Business Wire (press release)

SAN DIEGO, Sept. 6, 2017 /PRNewswire/ -- Renova Therapeutics, a biotechnology company developing gene and peptide-based treatments for cardiovascular and metabolic diseases, today announced that the company's co-founder Dr. H. Kirk Hammond is the recipient of the 2017 William S. Middleton Award, the highest biomedical laboratory research award in the U.S. Department of Veterans Affairs (VA).

The Middleton Award is given annually to recognize outstanding achievements in biomedical research. Dr. Hammond, a Professor of Medicine at UC San Diego and a cardiologist with the VA San Diego Healthcare System, received the award for his contributions to the understanding of mechanisms of cardiovascular disease and novel gene transfer treatments for angina and heart failure. Dr. Hammond is also investigating gene transfer for type 2 diabetes.

Dr. Hammond has authored more than 100 peer-reviewed publications related to cardiovascular disease and is an inventor on nine patents. He devised and led the Phase 2 clinical trial of AC6 gene transfer for the treatment of patients with heart failure and reduced ejection fraction. Results of the trial indicated that, through a one-time administration, AC6 gene transfer safely increased heart function beyond optimal heart failure therapy (JAMA Cardiology). This study was funded by the National Institutes of Health (NIH), the Gene Therapy Resource Program and Renova Therapeutics, via an NIH public-private partnership.

"If successful, these trials could lead to the first registration of a gene therapy product for treating heart disease," said Dr. Rachel Ramoni, VA's Chief Research and Development Officer. "Dr. Hammond is clearly a pioneer of intracoronary gene therapy and novel patient delivery mechanisms that will have a broad impact on the health care of veterans."

AC6 gene transfer is being developed by Renova Therapeutics as RT-100, its lead gene therapy candidate advancing to a Phase 3 clinical trial known as FLOURISH.

About heart failureHeart failure is a chronic disease characterized by the inability of the heart to pump sufficient blood to meet the body's demands. It is a progressive and fatal chronic condition, and symptoms worsen over time. Heart failure afflicts more than 28 million people globally and is the only cardiovascular disease that is increasing in prevalence. In the United States, it is the most common cause for emergency hospital admissions in patients 65 and older.

About Renova Therapeutics Renova Therapeutics is developing definitive, one-time gene therapies and peptide infusion treatments to restore the health of people suffering from chronic diseases. The first indications the company is pursuing are gene therapy treatments for heart failure and type 2 diabetes, two of the most common and devastating chronic diseases in the world. The company's lead product, RT-100, is a treatment that delivers a therapeutic gene directly to the heart during a routine outpatient procedure and has the potential to increase heart function in millions of patients with heart failure. The company's product pipeline also includes a groundbreaking gene therapy in preclinical stage for sufferers of type 2 diabetes, as well as a peptide infusion therapy for the treatment of acute decompensated heart failure. Renova Therapeutics was founded in 2009 and is led by an experienced management team in biopharmaceuticals and gene therapy. For additional information about the company, please visit http://www.renovatherapeutics.com.

References

View original content with multimedia:http://www.prnewswire.com/news-releases/renova-therapeutics-co-founder-awarded-highest-research-honor-by-the-us-department-of-veterans-affairs-300514250.html

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Renova Therapeutics co-founder awarded highest research honor ... - PR Newswire (press release)

Parent Project Muscular Dystrophy (PPMD) will host a one-hourwebinarat 2 p.m. Eastern Time on Wednesday, Sept. 6, that will focus on an upcoming clinical trial exploring gene therapy for Duchenne muscular dystrophy.

The webinar will be led by Dr. Jerry Mendell, who, together with fellow researcher Dr. Louise Rodino-Klapac, received a $2.2 million grant from PPMD in January 2017 for their gene therapy research project at the Nationwide Childrens Hospital in Columbus, Ohio.

The project is now approaching its first human trial, expected to begin in the next few months. Mendell will talk about how the trial is designed, including inclusion and exclusion criteria for participation. He will also share planned timelines.

Those wishing to participate are asked to register and submit questions in advance. Follow this link for more information about registering and submitting questions.

The grant was the first in the nonprofits Gene Transfer Initiative, which intends to support research into gene-therapy-based solutions. The webinar is part of a series that intends to present researchers and companies that focus on gene therapy for Duchenne.

Such therapies include gene transfer techniques, in which a small but functional version of the dystrophin gene, referred to as micro-dystrophin, is delivered with the help of a non-infectious virus. Other approaches use gene editing with the help of the CRISPR-Cas9 system (a naturally occurring bacterial defense system that has been adapted into a gene-editing tool).

The Nationwide Childrens Hospital trial will focus on the delivery of micro-dystrophin.

But while the webinar series will present research projects in various stages of progress, it spent the first parton Aug. 15 discussing what these approaches really mean, allowing patients and families to better understandthe complex science behind the therapeutic approaches. By understanding the science, PPMD hopes that families can make better choices once these therapies reach clinical trials.

PPMD also felt prompted to bring gene therapies to Duchenne patients with the recent FDA approval of Kymriah, the first gene therapy to be approved in the U.S.

While Kymriah is a cancer immunotherapy using a different approach than that likely to be used in Duchenne, the approval constitutes another piece of evidence showing the tremendous strides this technology has made since the 1990s and its early days of research, PPMDs Abby Bronson wrote in a blog post.

[The Kymriah] approval means that there are regulatory and commercial pathways for cell and gene based therapy. It means that you can put living DNA into a human and it can do its job, Bronson wrote in her blog. And it means that years of scientists making seemingly incremental advances can all come together and result into a giant step forward. A step forward that we believe will move this technology in a direction that will eventually benefit our community, our children.

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Upcoming Duchenne Gene Therapy Trial to Be Focus of PPMD-hosted Webinar on Wednesday, Sept. 6 - Muscular Dystrophy News

In 1990, geneticist William French Anderson injectedcells with altered genes into a four-year-old girl with severe immunodeficiency disorder. This was the first sanctioned test of gene therapy, in which genetic material is used to treat or prevent disease.

If were lucky, Anderson told The Chicago Tribune, with this little girl weve opened the door for genetic engineering to attack major killers and cripplers, particularly AIDS, cancer and heart disease.

Gene therapy has never fulfilled these grand hopes. In the decades since Andersons experiment, thousands of clinical trials of gene therapies have been carried out. But the first gene therapy was only approved for sale in the U.S. this week. The Food and Drug Administration announced its approval of Kymriah, a gene therapy produced by Novartis for a form of childhood leukemia. A few gene therapies have previously become available in China and Europe.

An FDA press release emphasizes the historic nature of the approval. Were entering a new frontier in medical innovation with the ability to reprogram a patients own cells to attack a deadly cancer, FDA Commissioner Scott Gottlieb says.

As I have noted in previousposts (see Further Reading), the hype provoked by genetic research has always outrun the reality. Gene-therapy proponents have long predicted that it will eliminate diseases such as cystic fibrosis and early-onset breast cancer, which are traceable to a defective gene, as well as disorders with more complex genetic causes.Enthusiasts also envisioned genetically engineered "designer babies" who would grow up to be smarter than Nobel laureates and more athletic than Olympians.

Gene therapy turned out to be extremely difficult, because it can trigger unpredictable, fatal responses from the body's immune system.The National Institutes of Health warnsthat gene therapy can have very serious health risks, such as toxicity, inflammation, and cancer.

Kymriah is a case in point. The FDA press release warns that Kymriah can cause life-threatening immune reactions and neurological events, as well as serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia). According to The New York Times, the FDA is requiring that hospitals and doctors be specially trained and certified to administer [Kymriah], and that they stock a certain drug needed to quell severe reactions.

Kymriah illustrates another problem with gene therapy: high cost. Novartis is charging $475,000 for Kymriah. As a recent Reuters article notes, over the past five years two gene therapies have been approved for sale in Europe, one for a rare blood disease and the other for the bubble-boy immunodeficiency disorder. The therapies cost $1 million and $700,000, respectively. So far, the companies that make the therapies have achieved a total of three sales.

As journalist Horace Freeland Judson points out in this excellent 2006 overview, The Glimmering Promise of Gene Therapy, biology and economics have conspired against gene therapy. Judsonnotes that most individual diseases caused by single-gene defectsthe kind that seem most likely to be cured by gene therapyare rare. (Sickle-cell anemia and some other hemoglobin disorders are among the few exceptions.)

Judson adds that because different diseases have different genetic mechanisms and affect different types of tissue, each presents a new set of research problems to be solved almost from scratch. As the millions burned away, it became clear that even with success, the cost per patient cured would continue to be enormous. And success had shown itself to be always glimmering and shifting just beyond reach.

The advent of CRISPR, a powerful gene-editing technique, has inspired hopes that gene therapy might finally fulfillexpectations. Researchers recently employed CRISPRin human embryos to counteract a mutation that causes heart disease. Potentially, The New York Times reported last month, the method could apply to any of more than 10,000 conditions caused by specific inherited mutations.

CRISPR has also renewed concerns about the ethics of engineering people with enhanced physical and mental traits. These concerns are grossly premature. As Science noted recently, CRISPR poses some of the same risks as other gene therapies. The methodstill has a long way to go before it can be used safely and effectively to repairnot just disruptgenes in people.And in fact questions have now been raised about the CRISPR research on embryos mentioned above.

Some day, applied genetics might live up to its hype, but that day is far from arriving.

Further Reading:

Could Olympians Be Tweaking Their Genes?

Have researchers really discovered any genes for behavior?

My Problem with Taboo Behavioral Genetics? The Research Stinks!

Hype of Feel-Good Gene Makes Me Feel Bad.

New York TimesHypes "Infidelity Gene."

Quest for Intelligence Genes Churns out More Dubious Results.

Warrior Gene Makes Me Mad.

Should Research on Race and IQ Be Banned?

Read more:
Has the Era of Gene Therapy Finally Arrived? - Scientific American (blog)

For a few thousand people around the world, reaching the age of 20 is a landmark to dread, not to celebrate.

Coping since birth with Leber Congenital Amaurosis (LCA), anyone with this genetic eye disorder who hasnt already lost their sight can expect to be legally blind before they reach 21 years of age.

Characterized by deep-set eyes that are prone to involuntarily, jerky movements, LCA is caused by a fault in one or more of about 14 genes so far identified. There is no proven treatment, although that may soon change.

In late August, biotech company Spark Therapeutics Inc. ONCE, +1.70% was granted a priority review of a treatment for LCA that may make it the first gene therapy approved for use in the U.S. by the Food and Drug Administration (FDA).

Read: Novartis CAR-T therapy was the first to be approved in the U.S.

The Philadelphia-based company will by Jan. 12 discover whether the FDA will issue a biologics license for Luxturna, which can replace the faulty RPE65 gene that causes LCA with a properly functioning copy. Should it be approved, victims of this disease will soon be able to receive a single injection that may permanently restore functional eyesight.

Gene therapys payoffs

While traditional research is usually focused on unlocking a way to treat one condition, gene therapies such as Luxturna may be game changers because they are based on platforms that can be adapted and used to tackle multiple inherited disorders.

Using similar techniques, Spark is also working on a functional cure for hemophilia, a disease that afflicts about 20,000 people in the U.S. and around 400,000 globally for which the market is worth about $8.5 billion in the U.S. and European Union.

In-human trials of SPK-8011 recently showed that Sparks therapy has the potential to lift the Factor VIII protein necessary for normal blood clotting to functional and sustained levels. In short, as with the Luxturna, the therapy has the potential to offer a one-shot cure.

That would be seismic for hemophiliacs, whose main option today is regular infusions of Factor VIII protein. Unfortunately, within a few days almost none of the protein remains in the body and the hemophiliacs blood is again unable to clot normally. Spark is also developing a treatment for hemophilia B, a much smaller market.

A new dawn

Biotech companies have reached this point because research has advanced to the stage where weve figured out how to identify the genetic causes of disease and how to apply that knowledge to develop therapies that will replace defective genes to provide a lasting cure.

Voyager Therapeutics Inc. VYGR, +24.70% is focused on gene therapies for neurological disorders such as Parkinsons, Huntingtons, Lou Gehrigs disease or ALS, Friedreichs ataxia (which damages the nervous system), Alzheimers and chronic pain.

In addition to cancer immunotherapy and the more controversial gene editing, bluebird bio Inc. BLUE, +0.84% has eight gene therapy programs, including research into adrenoleukodystrophy, or ALD, a deadly brain disorder that mostly affects boys and men; beta thalassemia; and sickle cell, none of which have a cure.

Should Spark, or another company such as BioMarin Pharmaceutical Inc. BMRN, -0.72% or Sangamo Therapeutics Inc. SGMO, -4.43% which are also working on hemophilia, succeed with its gene therapy, it could adversely impact suppliers of traditional Factor VIII protein infusions, such as Shire PLC SHP, +0.89% which had revenue from hemophilia treatments of $870.9 million in the first quarter of 2017.

Cost problems

Cost has been a headwind for the two gene therapies so far approved. In April, Fierce Pharma reported that uniQure NV QURE, +4.42% would not ask the European Medicines Agency to renew its marketing authorization for Glybera, the worlds most expensive drug at $1 million, when it expires in October, because in the four years after it gained approval in 2012 it was used commercially and paid for once, according to the MIT Technology Review.

Europes other approved gene therapy has fared no better. GlaxoSmithKline Plc GSK, +0.28% said in July it is seeking a buyer for Strimvelis, a treatment for a rare inherited immune deficiency, which took a year after approval to gain its first patient.

Perhaps the solution is a new payments system for ultra-expensive and long-lasting gene therapies, based on annuities for each additional time period of a treatments effectiveness.

But how do you measure cost? In December, Biogen Inc. BIIB, +0.48% gained FDA approval for Spinraza, a treatment for spinal muscular atrophy, the leading genetic cause of infant death in the U.S. Spinraza is priced at $375,000 a year for life (after $750,000 in the first year of therapy), while a one-shot gene therapy being developed by AveXis Inc. AVXS, +1.89% for SMA may provide a cure to someone who could go on to live 80 or more years. What sort of a premium for AveXis approach is justified?

Pricing is not dissuading biotech companies. There are about 7,000 genetic diseases, and the whole pharmaceutical and biotech industry is now working to solve each of those problems.

Investors seeking to benefit from a potential medical moonshot should consider allocating capital on a long-term basis to well-managed gene therapy companies with transformative assets that give them a competitive advantage.

Ethan Lovell is co-portfolio manager of the Janus Henderson Investors Global Life Sciences strategy.

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Opinion: How investors should play gene-therapy stocks - MarketWatch

Planned Parenthood, the embattled nonprofit health provider that specializes in reproductive health, has won the 2017 Lasker Award for public service.

The Albert and Mary Lasker Foundation also honored Dr. Douglas Lowy and John Schiller of the National Cancer Institute with its clinical research award for work that led to the development of a vaccine against human papillomavirus, which causes cervical cancer. Molecular biologist Michael N. Hall received the foundations basic medical research award for laying the scientific groundwork for advances in the treatment of cancer, diabetes, neurodegenerative disorders and diseases of aging.

The Lasker Awards, announced Wednesday, are given annually to recognize advancements in the prevention and treatment of disease. Each award carries an honorarium of $250,000. Dozens of past winners have gone on to win the Nobel Prize.

The Lasker-Bloomberg Public Service Award to Planned Parenthood comes at a time when the international organizations global mission has come under budgetary assault on Capitol Hill. The healthcare provider offers cancer screenings, testing for sexually transmitted diseases, birth control services and general care to millions of people each year. But the organization also provides abortion services, which makes it a frequent target of some lawmakers and others with antiabortion views.

Approximately one in five women in the U.S. have received its assistance at some point during their lives, the Lasker Foundation said in its award citation. Without Planned Parenthood, many individuals would not have access to high-quality and affordable health care.

Lowy and Schillers research on infection-fighting antibodies led to the development of a vaccine against human papillomavirus. The virus, also known as HPV, causes the worlds second-most common cause of malignancy in women, cervical cancer. In 2014, that work led President Obama to award Lowy and Schiller the National Medal of Technology and Innovation.

All of this years honorees acknowledged the changed political environment in which they conduct their activities. All warned that their work and other work like it would be squelched if the Trump administrations proposed restrictions on womens healthcare and cuts to basic biomedical research funding are adopted by Congress.

Planned Parenthood President Cecile Richards noted that her organizations founders, Dr. Margaret Sanger and Dr. Bessie Moses, were the first women to be awarded the Lasker prize for medicine for their contributions to contraception at a time when it was illegal in the United States. She marveled that more than 65 years later, the U.S. government has reprised its hostility to the policies that the work of Sanger and Moses made possible.

Were at a moment in the U.S. where there are major political efforts to get a rollback of reproductive care and reproductive rights, Richards said.

The scientists honored by the Lasker Awards offered more indirect criticism. They suggested that amid deep budget cuts in federal funding for biomedical research, scientists will not have the latitude to pursue research on subjects whose significance in not yet understood.

Basic science is the engine that drives important breakthroughs in public health, said Schiller, whose work led to the development of the first vaccine to prevent a cancer.

Its not clear which basic discoveries are going to lead to public health breakthroughs, he added. Its an example where we cant be too top-down in our research enterprise. You cant dictate which discoveries will be made.

Evan Vucci / Associated Press

National Cancer Institute researchers Douglas Lowy, left, and John Schiller, shown here with President Obama, have been awarded the Lasker Award for clinical research.

National Cancer Institute researchers Douglas Lowy, left, and John Schiller, shown here with President Obama, have been awarded the Lasker Award for clinical research. (Evan Vucci / Associated Press)

That was certainly the case for Hall, an American and Swiss scientist based at the University of Basel in Switzerland whose work has been translated into therapies for a variety of diseases.

He won his Lasker Award for his discovery of a protein called TOR (short for target of rapamycin) that tells cells when to grow, divide and survive. The gene that expresses TOR is found in organisms ranging in complexity from yeast to humans, and it often mutates in cancer cells. In mammals, who have a version called mTOR, its also a key player in activation of the immune system.

Halls elucidation of how TOR works has led to the use of a class of targeted cancer drugs called mTOR inhibitors, including rapamycin and mimics such as the drug everolimus (marketed as Afinitor), in the treatment of certain aggressive cancers of the kidney, breast or brain.

Faulty signaling in the mTOR network is implicated not only in cancer, but in a range of other diseases linked to aging, such as diabetes and brain diseases. That has led many to believe that understanding how TOR works will lead to insights that could extend the human lifespan.

Among the insights already gleaned: that in mice, at least, calorie restriction lengthens lifespan by inhibiting the activity of mTOR.

The basic research honored by this years Lasker Award was part of an international race among scientists to unravel a mystery: why (and how) did the drug rapamycin, an antifungal medication that emerged from soil harvested on Easter Island, also have the ability to suppress the proliferation of both cancer cells and immune cells in mammals?

Hall and his colleagues identified and sequenced the TOR1 and TOR2 genes in yeast, and published the result in the journal Cell in 1993.

melissa.healy@latimes.com

@LATMelissaHealy

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Lasker Awards honor Planned Parenthood and research on preventing and fighting cancer - Los Angeles Times

PUBLISHED: 18:08 31 August 2017 | UPDATED: 18:08 31 August 2017

Mia Jankowicz

The Gene and Cell Therapy Catapult is due to open in Autumn 2017. Picture: Daniel Buman

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The Cell and Gene Therapy Catapult is making its home at the Stevenage Bioscience Catalyst campus in Gunnels Wood Road, and is due to open in autumn 2017.

Now an extra 12 million in government funds will go towards fitting out the buildings second floor.

The centre had already attracted 55 million of funding in 2014 from the Department for Business, Innovation and Skills (now the Department for Business, Energy & Industrial Strategy).

The extra funds will double the centres capacity and at full capacity it is predicted to bring 1.2 billion in revenue by 2020.

Chief executive officer Keith Thompson explained to the Comet that Stevenage was a good fit for the site, with the towns closeness to airports as well as the presence of other scientific expertise all big positives.

We went through a very rigorous search across the UK for our site, said Mr Thompson.

Theres a strong pedigree of pharmaceuticals around the area.

Stevenages workforce also stands to benefit, with the potential creation of around 180 support jobs.

The Cell & Gene Therapy Catapult has a mission to accelerate the UKs cell therapy industry and to make Stevenage an industry world leader.

Currently, one problem holding up cell research globally is the low availability of the large numbers of cells needed to perform large-scale clinical trials.

The 7,200-square-metre facility will allow UK businesses that are developing new cell therapy treatments to use its labs to manufacture cells for clinical trials at a large scale.

Cell and gene therapies are showing potential worldwide to combat numerous illnesses.

At the frontier of medical science, cell therapy is a technique which involves the injection of living cells into the human body in order to repair the direct causes of genetic diseases.

For example, the Cell & Gene Therapy Catapult played a large role in the creation of modified cells that are trained to recognise a certain protein in leukaemia cells, and then attack and destroy the cancerous cells.

To find out more visit http://www.ct.catapult.org.uk.

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Stevenage-based Cell and Gene Therapy Catapult gets 12 million ... - Comet 24

Could junk DNA protect our hearts?

Scientists at the University of California at Los Angeles and the Howard Hughes Medical Institute reported that they successfully used gene therapy to lower cholesterol in mouse models of familial hypercholesterolemia. The gene they used, called LeXis, was once considered junk DNA because it seemed to serve no purpose. But when the researchers gave the mice LeXis and then fed them a high-cholesterol diet for 15 weeks (think cheeseburgers and fries), their cholesterol went down, artery blockages opened up andless fat appeared to build upin their livers. The research was published in the journal Circulation. Release

Researchers at the Francis Crick Institute have discovered that acute myeloid leukemia (AML) causes bone marrow to leak blood, which in turn impedes the proper delivery of chemotherapy. So they tried mixing chemo with experimental drugs designed to treat heart and blood vessel disorders, and the results were promising. In mouse models of AML and in human tissue samples, the heart drugs stopped the leaks and the chemo became more effective, the researchers reported in the journal Cancer Cell. They believe the findings may point to a potential new combination of treatments for AML. Release

Researchers at Columbia University have completed mouse studies suggesting that a hormone produced by bone cells, osteocalcin, may be useful in reversing memory loss that occurs as part of aging. They gave aged mice continuous infusions of the hormone for two months and observed improvements on two different memory tests. Similar results were seen when the mice were given plasma from young mice, which have naturally high levels of osteocalcin. They plan to do more research to determine whether their findings, published in the Journal of Experimental Medicine, can be translated to drug therapies for people. Release

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News of NoteGene therapy to protect the heart; boosting chemo with cardio drugs; reversing memory loss - FierceBiotech

FINDINGS

Scientists from UCLA and the Howard Hughes Medical Institute successfully used a gene that suppresses cholesterol levels as part of a treatment to reduce plaque in mice with a disorder called familial hypercholesterolemia. In a preclinical study, researchers found that the gene, LeXis, lowered cholesterol and blockages in the arteries, and the treatment appeared to reduce the build-up of fat in liver cells.

Familial hypercholesterolemia is an inherited condition characterized by extremely high levels of low-density lipoprotein cholesterol (commonly referred to as bad cholesterol) and an increased risk of early heart disease.

The LeXis gene belongs to a unique group of genes that until recently were considered junk DNA because scientists believed they served little purpose. However, evidence from the human genome project led to the discovery that genes like LeXis are actually active. The study of these genes,now referred to as long noncoding ribonucleic acids, or lncRNAs, is a rapidly evolving area in biology.

Researchers wanted to test whether a single injection of LeXis could slow the development of heart disease. To do so, they gave the mice either LeXis or a control gene, and fed them a 15-week diet consisting of food high in sodium and cholesterol the mouse equivalent of fast-food hamburgers and french fries. Researchers then measured the progression of heart disease.

In the next phase of the study, researchers intend to confirm the findings in larger animals and test the therapy in combination with currently available treatments.

Although previous research has shown that lncRNAs can be important, this is the first study to show that they could potentially be used to treat a human disease using gene therapy. Junk genes could one day offer a framework for treating people with familial hypercholesterolemia and other conditions that are otherwise very difficult to treat.

The papers authors are Xiaohui Wu, Zhengyi Zhang and Dr. Tamer Sallam of UCLA; and Dr. Peter Tontonoz, Marius Jones and David Salisbury of the Howard Hughes Medical Institute.

The study waspublished onlinein the journal Circulation.

The research was supported by grants from the National Heart, Lung, and Blood Institute; the American College of Cardiology; and the Lauren B. Leichtman and Arthur E. Levine UCLA Cardiovascular Discovery Fund.

Learn more about the cardiovascular research theme at UCLA.

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Gene therapy using 'junk DNA' could lower risk for heart disease - UCLA Newsroom

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Penn Medicine researchers made huge strides in the medical world Wednesday when the Food and Drug Administration approved a gene-altering cancer treatment that they designed. It's the first of its kind to be approved.

The therapy is marketed as Kymriah and made by Novartis, but was originally developed at Penn by Carl June, a Penn Medicine professor in immunotherapy, and his team, The New York Times reported. The treatment, which is the first-of-its-kind in the United States, uses the patient's genetically altered immune cells to fight the disease.

The FDA called the gene therapy a "historic" act.

Timothy Cripe, an oncologist with Nationwide Children's Hospitalin Columbus, Ohio, referred to the research as the "most exciting thing I've seen in my lifetime," The Washington Post reported.

The treatment is meant for children and young adults with B-cell acute lymphoblastic leukemia, especially those who don't respond well to traditional treatment methods.

According to the New York Times, the first child to receive the therapy was Emily Whitehead in 2012. Whitehead was severely ill from leukemia in 2012, but after treatment, has been free from cancer for more than five years.

Penn researchers have been working on approving this treatment method for years. In 2011, the results of the CAR-T cell therapy, as the treatment was initially called, were published in the New England Journal of Medicine and Science Translational Medicine by June and his team. It was the first demonstration of the use of gene transfer therapy to create serial killer T cells targeting cancerous tumors, according to a press release by the Penn medical school.

A year later, the University partnered with Swiss pharmaceutical company Novartis to continue research on immunotherapy research. At the time, the collaboration was the largest academic-industry agreement in Penns history.

In 2016, Penn Medicine, along with five other peer institutions, partnered with The Parker Institute for Cancer Immunotherapy after receiving a $250 million grant to develop new techniques for cancer treatment.

Novartis said the gene-therapy would cost $475,000 and would be available at an initial network of 20 approved medical centers, as the treatment is hard to administer.

I have to keep pinching myself to see that this happened, June said to The New York Times. It was so improbable that this would ever be a commercially approved therapy, and now its the first gene therapy approved in the United States. Its so different from all the pharmaceutical models. I think the cancer world is forever changed.

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A 'historic' cancer treatment designed by Penn researchers just got approved by the FDA - The Daily Pennsylvanian

Personalized cancer treatments known as CAR-T cells (chimeric antigen receptor T cells) have dominated the headlines lately, thanks to Novartis tisagenlecleucel, which won an early approval from the FDA for the treatment of leukemia on Aug. 30. But CAR-T treatments are labor-intensive and expensive to make, and they can attack healthy tissues in the body, leading to dangerous side effects.

Scientists at the Fred Hutchinson Cancer Research Center have developed a tool that they believe could address both those shortcomings of CAR-T and other forms of cell engineering. They have invented nanoparticles that deliver proteins to cells, which in turn edit those cells genes temporarily. Lead author and bioengineer Matthias Stephan describes it as hit-and-run gene therapy, and he believes the technique will streamline the manufacturing of cell-based therapies.

Heres how it works: The nanoparticles home in on specific cells, such as the T cells in the immune system. They then deposit messenger RNA (mRNA) to those cells, which triggers short-term changes in the proteins the genes produce. The technology does not permanently change the DNA, but it makes enough of an impact on it to produce a therapeutic outcome.

RELATED: Can CAR-T cancer treatments be fine-tuned to avoid toxic side effects?

Whats more, the nanoparticles can be freeze-dried and then activated with a small amount of water. They really let you fulfill all your wishes as a genetic engineer because you can pack in all your different [gene-therapy] components and further improve the therapeutic potential of your cell product without additional manufacturing steps, Stephan said in an article posted on Fred Hutchs website.

Stephans team proved out their concept by testing the nanoparticles in three different cell-engineering applications, one of which was CAR-T. Currently, CAR-T treatments are made by giving T cellsgenes that teach them to destroy cancer cells. The Fred Hutch scientists used their nanoparticles to remove a different gene from T cellsone that normally prompts them to attack healthy tissue.

Then they tried enhancing the CAR-T cells in a different manner. They temporarily gave them genes that have the potential to make central memory T cells, which are able to survive over the long term, remembering their cancerous targets and attacking them should they ever resurface.

The scientists tested their engineered CAR-T cells in mouse models of leukemia and found that the animals that received them lived twice as long as mice that got conventional CAR-T cells. They also tested the nanoparticles in two other cancer-related applications of gene therapy.

Despite all the excitement over CAR-T, concerns about side effects continue to dog the field. A dangerous immune reaction known as a cytokine storm has been seen in trials of both Novartis treatment and Axi-Cel, a CAR-T from Kite Pharma, which is being acquired by Gilead. The third player in the CAR-T field, Juno Therapeutics, saw its late-stage trials delayed when some patients died of neurological side effects.

Fred Hutch scientists have been working on other techniques for improving CAR-T. In December, a set of researchers there who receive funding from Juno announced positive results from a trial of a fine-tuned CAR-T treatment in patients with chronic lymphocytic leukemia (CLL). Instead of using just one type of CAR-T, the team combined two specially selected cell subtypes into one treatment. They also announced they had identified biomarkers that they believe can be used to predict which patients are likely to have severe reactions to the treatment.

Stephans team is now collaborating with several companies to fine-tune CAR-T treatments for cancer, according to Fred Hutch. And they believe their freeze-dried nanoparticles may prove useful in developing treatments for a range of other diseases, too, including HIV and blood disorders caused by defective hemoglobin.

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'Hit-and-run' gene therapy nanoparticles could enhance CAR-T ... - FierceBiotech