Gene Therapy Products
Suicide Gene Therapy: The Genetic “Kill Switch”
What it is?
Suicide gene therapy is based on the introduction of a viral or a bacterial gene into tumor cells, which allows the conversion of a non-toxic compound into a lethal drug.
Basically suicide gene therapy also known as Gene Directed Enzyme/Prodrug therapy (GDEPT) or as Gene Prodrug Activation Therapy (GPAT) uses viral vectors to deliver suicide genes into tumor cells which possess the enzyme that converts prodrug to active metabolites, it increases the toxicity level several fold inside the tumor whereas the vast majority of the host cells are unaffected. Thus it accomplishes the same end goal of chemotherapy treatments, but by different means. While chemotherapy targets all of the body’s rapidly dividing cells with the intention of killing cancer cells, suicide gene therapy delivers a cancer-killing drug solely to tumors. This bypasses chemotherapy side effects like hair loss and nausea, which are caused by collateral damage to non-cancerous cells.
How it works?
There are several suicide gene therapies. Among them Herpes Simplex Virus thymidine kinase (HSV-tk) and Cytodine Deaminase (CD) are important. The Herpes Simplex Virus deposits a gene into the cancer cells that causes them to produce a special enzyme. Once the virus triggers production of the enzyme, doctors initiate step two by injecting the patient with a unique type of chemotherapy drug called a prodrug. Suicide gene therapy typically uses ganciclovir (GCV) and its nucleoside analogs (acyclovir etc). When administered, GCV and other prodrugs are nontoxic, and thus cause no harm to healthy cells.
But when GCV comes in contact with the special enzyme, the prodrug turns highly toxic. This starts a natural biological process called programmed cell death, which causes cells to commit suicide. Because HSV-tk and CD are not present in any of the body’s healthy cells, the prodrug only destroys cancer cells that were genetically altered by the virus.
Although only a limited number of tumor cells will take in HSV-tk or CD from the virus, the activated prodrug is passed on to neighboring cells through what doctors call the bystander effect. Further, cells that destroy themselves as a response to treatment attract immune cells that clear the tumor site of dead and dying cancer cells.
Limitations of (HSV-tk)-GCV system
This HSV-tk system suffers from limitations which include (i) the potential for production of inactive catalytic molecules due to the utilization of alternative splicing sites, (ii) the potential immunogenicity of the viral enzyme, (iii) the potential need to administer GCV to control cytomegalovirus infections (a complication often encountered in allo-HSCT) and thus cause unintended elimination of HSV/Tk-engineered cells, and (iv) the requirement for active cell division in order to mediate cell death, which takes time and renders the system less effective for use in post mitotic cells. Moreover, major improvements are needed in vector design to enhance targeting and delivery of suicide genes.
Live and Let Die: A New Suicide Gene Therapy
Despite of the limitations associated with HSV/tk-GCV system suicide gene therapy holds enormous potential in the eye of the researchers which is evident from the research done on combining suicide gene therapy with other treatments, improving the bystander effect and finding the optimal method for delivering GCV and the HSV-tk gene. One such example is iCasp9 (a late executor of the intrinsic pathway of apoptosis, leading to DNA fragmentation and rapid cell death) which represents more than a simple upgrade of the HSV/Tk-GCV system as it is not dependent on DNA synthesis as is HSV/Tk-GCV, allowing application in non-replicating cells. It involves dimerization of the subunits which is induced by addition of a biologically inert small molecule (AP1903) that has been shown in clinical studies to be well tolerated. Dimerization of iCasp9 activates one of the last steps in the apoptotic cascade, resulting in rapid cell death—as soon as 30 minutes after administration of the activator.
The field of suicide gene therapy is rapidly maturing and will no doubt be part of the future of cancer therapeutics. In addition, combination of Gene & Cell therapy approaches like “chimeric antigen receptors” or CARs for short also hold great promise for increasing the effectiveness of current chemotherapeutic treatment regimens.
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Only a hundred and fifty years have passed since Gregor Mendel’s discovery of simple Mendelian inheritance. In a remarkably short amount of time humans have achieved such impressive feats as sequencing the entire human genome and gaining understanding of the causes of most genetic disease. Now that researchers have all this information at hand, the focus has shifted to the design of reagents that can target specific genomic sequences. The rapid advancement of genome-editing techniques holds much promise for the field of human gene therapy. From bacteria to model organisms and human cells, genome editing tools such as zinc-finger nucleases (ZNFs), TALENs, and CRISPR/Cas9 have been successfully used to manipulate the respective genomes with unprecedented precision. With regard to human gene therapy, it is of great interest to test the feasibility of genome engineering because of their ease of customization and high-efficient site-specific cleavages that could potentially be used to treat a variety of human genetic disorders such as hemoglobinopathies, primary immunodeficiencies, and cancer.
Unraveling the potential of CRISPR-Cas9 for gene therapy
The molecular machinery from the prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas immune system has broadly been repurposed for genome editing in eukaryotes. In particular, the sequence-specific Cas9 endonuclease can be flexibly harnessed for the genesis of precise double-stranded DNA breaks, using single guide RNAs that are readily programmable. The endogenous DNA repair machinery subsequently generates genome modifications, either by random insertion or deletions using non-homologous end joining (NHEJ), or designed integration of mutations or genetic material using homology-directed repair (HDR) templates. This technology has opened new avenues for the investigation of genetic diseases in general, and for gene therapy applications in particular.
Patent Litigation over control of the revolutionary CRISPR-Cas9 tech
Despite the predicted utility of a successful gene editing technique, many current methods like Zinc Fingers Nucleases and TALENs have confounding issues like low efficiency, time-consuming procedures, and lack of specificity for both model organisms and humans. In the past several years, a new gene editing system viz, CRISPR-Cas9 derived from bacteria, has arisen as a frontrunner for efficient and successful gene editing.
Research in the area of CRISPR/Cas9 is gaining speed and this system could very well be the solution to many medical issues we face today. For evidence of CRISPR/Cas9’s promise, look no further than its attendant battle over intellectual property. Novartis and Atlas Venture joined together to form Editas Medicine, but a breakup of co-founders led Berkeley’s Jennifer Doudna to take her IP to the competing Intellia Therapeutics, while Swiss rival CRISPR Therapeutics has conflicting claims of its own backed by Versant. And now a team at Johns Hopkins has done some experiments to demonstrate its promise in engineering human stem cell therapies.
This proves that gene editing has staggering potential and that it can be developed as a naturalistic method of correcting defective genes by getting at the underlying causes of a broad range of diseases.
Gene Therapy’s fruition?
The world of gene therapy in which single-dose treatments correct debilitating defects enjoyed something of a renaissance in 2014. Strong clinical results from leaders in the once-maligned field spurred renewed optimism, helping a new generation of startups secure millions in venture financing to develop their next-generation approaches to the field. And that led to something of a trickle-up phenomenon in the industry, as the innovations of biotechs and academics convinced the world’s biggest players to give this field a second look. Now Bayer, Pfizer, Biogen Idec and Astellas are among the many companies toiling in gene therapy, joining high-profile biotechs like bluebird bio and uniQure.
DelveInsight’s Reports have already established a reputation of offering the affordable and comprehensive industry coverage and “on-the-ground” analysis in virtually every region of the world. These reports provide complete information for over 300 gene therapies which are in the pipeline for various therapy areas like; Oncology, Genitourinary, Dermatology, Central nervous system, Genetic Disorders, Hematological disorders, Metabolic disorders, Ophthalmology, Cardiovascular disease, Respiratory , Immunology, and many more…
DelveInsight’s Gene Therapy Reports cover the entire gene therapy market scenario including technology assessments, licensing opportunities, collaborations, market trends, pipeline coverage and competitive landscape. The report essentially provides DelveInsight’s proprietary market and pipeline analytics which identifies the front runners of all therapeutic areas. It also identifies the potential market movers and future regulatory landscape. These reports are designed to provide the clients with the means to out produce their competitors by developing a product that makes history.
For more info on Gene Therapy Reports for various Therapeutic areas contact us at: firstname.lastname@example.org.
Gene Therapy: Eye for the cure!
Recent technical advances have led to the demonstration of the molecular basis of various ocular diseases. Gene transfer into ocular tissues has been demonstrated with growing functional success and may develop into a new therapeutic tool for clinical ophthalmology. There are prospects for commercially available gene therapies for retinal disease in the near future and one thing is for certain that the future is brighter for thousands of patients with inherited retinal degenerations potentially amenable to treatment with this technology.
About Gene Therapy
Gene therapy is the addition of new genes to a patient’s cells to replace missing or defective copies, to restore or impart a new function to overcome a disease usually of genetic origin. Over the past several years, the unlocking of the human genome and the discovery that certain genes, or lack thereof or genetic defects therein, can be the cause of certain diseases has led to the ability to identify genes associated with retinal and other ocular diseases. According to the eyeGene National Ophthalmic Disease Genotyping Network, more than 100 ocular gene types have been identified, and the number increases yearly. To date, the genes for some 35 ocular disorders have been identified. Ophthalmologic disorders are responsible for 48% of the population becoming totally blind. In addition, more than 60 million people suffer from glaucoma and an increasing aging population is also resulting in more people suffering from refractive errors. It is estimated that in the U.S. and Europe, refractive errors affect more than 30% of the population aged 40 or older. Ocular gene therapy research has made rapid progress in the past few years. Although laboratory and animal experiments started were successful many years ago, the application in human beings took very long due to several biological and regulatory hurdles. However, the recent successful gene therapy clinical trials are promising and encouraging.
Gene Therapy: Role in Ophthalmological disorders
The eye is an attractive target for gene therapy because of its accessibility and its immune privilege. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma.
Current and possible candidates for gene therapy in the field of Ophthalmological disorders include Leber’s Hereditary Optic Neuropathy (LHON) (Leber optic atrophy), Juvenile Macular Degeneration (Stargardt Disease) and Ocular Pain etc. The three main types of gene therapies used in the field of ophthalmological disorders are gene replacement for loss-of-function mutations, gene knockdown for gain-of-function mutations, and gene enhancement/knockdown for non-monogenic diseases. However, all of these approaches have historically been subject to the same limitations: 1) how to deliver the vector into the affected cells 2) how to achieve broad distribution throughout the tissue of interest 3) how to maintain persistent transgene expression and functional rescue and 4) how to avoid both local and systemic toxic responses. Inspite of this gene therapy holds the promise of curing ocular diseases, and improving the quality of life for millions who suffer from visual impairments.
Gene Therapy: The Market Scenario
Many companies are investing in and researching on this field using gene therapy due to its promising effects. Large Pharmaceutical and Biotech giants, such as Applied Genetic Technologies Corporation (AGTC), Oxford Biomedica, and Pfizer etc., are operating in the field of ophthalmologic disorders in the gene therapy domain. A growing number of partnership between companies in drug development for example between Sanofi and Oxford Biomedica etc., are driving the new gene therapy research. The industry’s collective pipeline is brimming with 300+ therapies for various therapeutic areas. The recent success of gene replacement therapy for ophthalmological disorders is a big step forward in the field of genomic medicine. These results have enthused the medical community and basic scientists equally and have unveiled the potentials that is in store for the future of medicine. Once these experiments are refined and tailored to the needs of these patients with unambiguous success, nearly 500 eye genetic diseases and 1500 genetic diseases in other parts of the body could be potentially cured.
DelveInsight’s Gene Therapy Reports
DelveInsight’s Gene Therapy Reports cover the entire gene therapy market insights for ophthalmologic disorders including technology assessments, licensing opportunities, collaborations, market trends, pipeline coverage and competitive landscape. The report essentially provides DelveInsight’s proprietary market and pipeline analytics which identifies the front runners in this therapeutic area. It also identifies the potential market movers and future regulatory landscape.