OctopusyX BioConsulting (Olivier REVELANT, @octopusyx2), a member of Eurobiomed, and BioPharmAnalyses (Anne-Lise BERTHIER, @anneliseberthie) are proud to announce the launch of their new report entitled "AAV-based Gene Therapy Products: Ongoing Clinical Trials". CD19: . To get there, you'll need a process that's scalable and cost effective. Development of a comparability strategy should be incorporated during product development to minimize risks to future approvals. The guidance provides examples of different gene therapy products and what the agency expects . Adeno-Associated Virus Vectors in Gene Therapy Unmet Needs. Indeed, two AAV-based gene therapy products are already on the market and being used to treat spinal muscular atrophy type-1 (Zolgensma), a debilitating neuromuscular disease, and Leber congenital amaurosis type-2 (Luxturna), a retinal dystrophy that causes blindness. China was the first country in the world that has approved commercial gene therapy products. As of 2020, over 30,000 patients have . OctopusyX BioConsulting (Olivier REVELANT, @octopusyx2), a member of Eurobiomed, and BioPharmAnalyses (Anne-Lise BERTHIER, @anneliseberthie) are proud to announce the launch of their new report entitled "AAV-based Gene Therapy Products: Ongoing Clinical Trials". . With an extensive viral tropism profile, an AAV vector is particularly beneficial as a transfer mechanism for gene therapies involving the heart, liver, and central nervous system, Signal Transduction and Targeted Therapy notes. Silver Spring, MD 20993. Producing gene therapies relies on the successful introduction of genetic material into viral vectors, most commonly adeno-associated viruses (AAV). The first product was called Gendicine. Your adeno-associated virus (AAV) gene therapy deserves to be a success. Quantitative PCR (qPCR) is one of the common methods to quantify the AAV vector titre, but different variables can lead to inconsistent results. AAV vector construction and administration. High quality and high purity reference materials (empty capsids) can be used as negative controls or reference materials in quality control assays, including HPLC, ELISA, etc. China was the first country in the world to approve a commercial gene therapy product. Scalable manufacturing solutions for adeno-associated virus (AAV) viral vectors are needed to meet the clinical and commercial production demands for gene and gene-modified cell therapies to help them advance rapidly through the clinic and to the market. Key Endpoints of Adeno-Associated Virus Vectors in Gene Therapy Treatment. Many gene therapy products, viral vector-based gene therapies in particular, have received approval in the clinic for managing a broad array of diseases including not only genetic disorders but other indications such as cancer and . Here we review the growing body of literature that describes both the design and development of ocular gene therapy products, with a particular emphasis on target and vector selection, and chemistry, manufacturing, and controls. The major research focus has been to develop effective gene delivery approaches to target the entire nervous system, using adeno-associated virus (AAV) vectors, for treating neuropathic lysosomal storage diseases in humans. Adeno-Associated Virus Vectors in Gene Therapy Marketed Products. . 1 Viral vectors are tools commonly used in genetics as they enable the movement of genetic material inside cells in a process called transduction . AAV manufacturing solutions for gene therapy commercialization. The present article reviews the current state of AAV use in gene therapy clinical trials for IRDs, with a brief background on AAV and the reasons behind its dominance in ocular gene therapy. Your adeno-associated virus (AAV) gene therapy deserves to be a success. Gendicine delivers a p53 gene into tumor cells. Scalable, cost-efficient, and robust filtration and chromatography-based processes are required for AAV purification. 11.2. . Real-time PCR based assays provide accurate, actionable results in hours, while meeting sensitivity . Gene therapy products exploit the biology of viruses, transferring the genetic sequences from a therapeutic into targeted cells. We do not work with or sell wild-type AAV. . Significant progress has been experienced in the field of Gene Therapy Medicinal Products (GTMPs), specifically with the use of AAV vectors. LAS VEGAS, Jan. 25, 2021 /PRNewswire/ -- The AAV Vector-Based Gene Therapy market size is anticipated to shoot up exponentially attributing to an increase in the approval of a growing number of . What gene therapy developers desperately need is a production platform that can produce viral vectors . This individual will be responsible for managing a team providing oversight to the numerous CMOs for manufacture of AAV, cell therapy products, and any other critical starting material or intermediate required in the manufacture of our products. Recombinant adeno-associated virus (rAAV) vectors are widely used for gene therapy because of several unique advantages, including long-lasting gene expression, wide tropism for mammalian cells, modest immunogenicity, non-pathogenicity, and no genome integration.1, 2 rAAV contains a single-stranded genome, which is protected by an icosahedral shell made of three different . In this presentation, regulatory as well as scientific specificities regarding manufacturing and quality control of GTMPs will be highlighted and the very recent activities initiated to foster the . Although GT is conceptually attractive, adverse and even fatal . Rapid growth in AAV and Lentivirus as vectors of choice in GT. We currently have three lentiviral-based gene therapies and one AAV-based . Glybera is composed of an adeno-associated virus serotype 1 (AAV1) viral vector with an intact copy of the human lipoprotein lipase (LPL) gene for delivery to muscle cells. 111 active CAR T cell investigations in OTAT as of 6/30/18. . Pfizer is committed to leading in this space by bringing together the foremost expertise in vector design and development with in-house knowledge of disease biology and manufacturing capabilities. Removal of impurities and separating empty from full . AAV formulation and drug-product workflows prioritize preformulation development, including buffer compatibility, freeze-thaw, and stability studies. We have entered into multiple gene therapy . Adeno-associated virus (AAV) is the most widely used viral vector for in vivo gene therapy applications. Some of the viruses that have been Make it happen — tap into knowledge on AAV virus transfection, AAV chromatography, and AAV analytics. . 2019, Cell & Gene Therapy Insights 2019; 5(4), 537- 547 Gene therapy is the therapeutic delivery of nucleic acid into a patient as a drug to treat disease. This >200 pages report provides a unique exhaustive overview of 116 ongoing trials for the treatment of 40 diseases (as of June . Adeno-associated virus (AAV) is the most common viral vector used in gene therapy products due to demonstrated safety, low immunogenicity and long-term transgene expression. The Food and Drug . Adeno-associated virus - or AAV - has been used in 100+ gene therapy clinical trials ( 1). United States. Fu lab is a translational biomedical research lab. /PRNewswire/ -- Addressing the need to make adeno-associated virus . Analysis of AAV gene therapy trials. This >200 pages report provides a unique exhaustive overview of 116 ongoing trials for the treatment of 40 diseases (as of June . 11. AAV Reference Materials (Empty Capsids) Recombinant adeno-associated virus (rAAV) is a widely used gene delivery tool for research and clinical applications. (BOSTON) — Adeno-associated viruses (AAVs) have become promising vehicles for delivering gene therapies to defective tissues in the human body because they are non-pathogenic and can transfer therapeutic DNA into target cells. The product is an adeno-associated virus type 9 (AAV9) vector containing the insertion of MBL2 3'UTR gene. Adeno-associated Virus (AAV) for Gene Therapy Figure adapted from: Li, et al. Laurence Guianvarc'h, PhD, Head, Upstream Development,Genethon. China was the first country in the world that has approved commercial gene therapy products. To ensure safe and effective gene therapy using adeno-associated virus as a delivery vector, the product must meet a set of quality attributes including concentration and content. Recent breakthroughs in genome editing tools and the combined use with AAV vectors have introduced new therapeutic modalities using somatic gene editing strategies. This table shows a synthesis of the productivity, the total number of doses per bioreactor, the cost per dose and the volume of culture . However, while the first gene therapy products approved by the Federal Drug Administration (FDA) use AAV vectors and others are likely to follow, AAV vectors still have not reached their full . Authors . . . Two AAV-based gene therapy products have already obtained the go-ahead from US and European health authorities: Luxturna® received FDA approval in December 2017 as a one-time gene therapy to restore functional vision in children and adult patients with biallelic mutations of the RPE65 gene (Leber congenital amaurosis, retinitis pigmentosa). It will also discuss pre-clinical progress in AAV-based therapies aimed at treating other ocular conditions that can have hereditable links, and what . Drug Name: Company Name. . Gene therapy has shown promise for the treatment of rare diseases, yet current clinical stage gene therapy products are not targeted and are generally based on one of a few AAV vectors that are . Adeno-Associated Vector or AAV) are defined, whether as a Drug Product (DP) or Drug Substance (DS). 4 The AAV gene therapy products that are in clinical evaluation target a variety of diseases affecting multiple organ types in varying patient populations. Recent publications in Molecular Therapy1 and Human Gene Therapy2 identify acute toxicity of adeno-associated virus (AAV)-mediated survival of motor neuron (SMN) or GFP expression, which warrants careful consideration to better understand the observation as well as the need to perform well-controlled studies to address this finding. . The AAV vectors for muscle- and liver-specific gene therapy were as described. We currently have 3 industry-leading phase 3 clinical gene therapy programs and have invested over $800M to expand our AAV manufacturing capacity. Key for a successful process are high overall yields and efficient removal of empty capsids and other impurities. The FDA gene therapy guidances released in early 2020 will have dramatic impacts to the path to commercialization for gene therapy companies. Make it happen — tap into knowledge on AAV virus transfection, AAV chromatography, and AAV analytics. Typical cells used are HEK-293, HeLa, Vero, and SF9. Gene Therapy and Gene Editing Gene therapy (GT) products mediate their effects by transcription or translation of transferred genetic material, or by specifically altering host genetic sequences Common gene therapy products: -Plasmids -Viral / bacterial vectors -Ex vivo genetically modified cells -Gene edited (GE) products Pox 6% AAV Due to these characteristics, along with the ability to target specific tissue types, recombinant AAV has become one of the main viral vectors used for research and gene therapy applications. AAV is a kind of non-enveloped virus with a linear single-stranded DNA genome. Figure 5: Number of in-vivo AAV gene therapy products under different stages of development, by disease area. This case study theoretically compares 3 processes in 500 L bioreactors with FectoVIR®-AAV, PEIpro® and another commercially available PEI transfection reagent to achieve the same viral titer yield: 8,8×10 18 VG needed to produce 1000 doses of Zologensma®. Removal of impurities and separating empty from full . List of Adeno-Associated Virus Vectors in Gene Therapy Marketed Drugs in the 7MM. Web page Relevant guidelines; Cell-therapy and tissue engineering: The overarching guideline for human cell- based medicinal products is the guideline on human cell-based medicinal products (EMEA/CHMP/410869/2006); Reflection paper on stem cell-based medicinal products (EMA/CAT/571134/2009); Reflection paper on in-vitro cultured chondrocyte containing products for cartilage repair of the knee . Epub 2018 Oct 7. Data from the clinical trials . The role of HPLC in analysing AAV gene therapy vectors. Over time, costs of goods will decrease in a manner similar to other new technologies with additional effort and inventive approaches. Gene therapy is a method of human disease treatment by introducing or changing a therapeutic genetic fragment in host cells, which has revolutionized the current treatment state of some incurable diseases. The first product was called Gendicine. The long-term safety of AAV gene therapy for haemophilia has so far been favourable both in the clinic and large animal models but needs continued attention. A number of different components, including cells, viral vectors, and plasmids, comprise the final cell and gene therapy products. However, while the first gene therapy products approved by the Federal Drug Administration (FDA . products is underway. Spurring on Gene-Therapy Development: Several pharmacological challenges hamper the clinical development of AAV-based products, Chemuturi explained. An overview of single use manufacturing for the production of AAV gene therapy products with comparisons to traditional monoclonal antibody production. Members of the Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) will discuss the toxicity risks of adeno-associated virus (AAV) vector-based gene therapy products at a Sept. 2-3 public meeting.The discussion will also address oncogenicity risks due to vector genome integration and safety issues identified during preclinical and/or clinical evaluation. Draft Guidance for Industry (July 2018) 23. www.fda.gov. Since the dawn of the era of human gene therapy research in the 1970s, hardly any vehicle for therapeutic gene transfer has attracted more attention than the Adeno-associated virus (AAV). An AAV is a dependoparvovirus that generally relies on an adenovirus or another helper virus for its genetic expression. protein outer shell. As a non-pathogenic member of the Parvoviridae family, AAV is composed of a single-stranded DNA genome encapsidated in a 23-28 nm, T = 1, non-enveloped . It can deliver its genetic material to . I will review the reasons for starting and the challenges of being the in-house . Gene of interest integrated into a viral vector The comparability problem could be solved by the availability of suitable standard material for the analytical characterization of AAV gene therapy products. Glybera is composed of an adeno-associated virus serotype 1 (AAV1) viral vector with an intact copy of the human lipoprotein lipase (LPL) gene for delivery to muscle cells. 11.2.1. Our passion is to solve the bottleneck problems in AAV gene therapy and find more better cu 2 -4 Briefly, for muscle gene therapy, the vector contained the canine FIX cDNA under transcriptional control of the cytomegalovirus (CMV) immediate early (IE) enhancer/promoter, a chimeric β-globin/CMV intron, and the human growth hormone (hGH) poly(A) signal. Two out of four gene therapy products currently approved by the FDA use AAV for gene delivery ( 2). Over time, costs of goods will decrease in a manner similar to other new technologies with additional effort and inventive approaches. ZOLGENSMA (onasemnogene abeparvovec-xioi) Novartis Gene . As the gene therapy field grows, drug developers are confronted with the fact that most gene therapy products can't be produced at the scale needed to meet growing demands. As the gene therapy field grows, drug developers are confronted with the fact that most gene therapy products can't be produced at the scale needed to meet growing demands. Wyatt's solutions for characterizing a variety of gene therapy products are described in the brochure Characterization of Biologics and Complex Drugs. To sustain this, reliable, fast, robust, GMP compliant process development strategies are needed. Data from the clinical trials . Genemedi help scientists from academic to industry in vectors optimization, scalable production, process development and technology transfer. AAV Vector-Based Gene Therapy. <p>While the ideal path during product development would be to avoid process changes, especially during later phases of clinical development, manufacturing changes are common in gene therapy products for many reasons. We currently have three lentiviral-based gene therapies and one AAV-based . 9. AAVnerGene Inc is an innovative company specialized in AAV technologies. Whilst FDA approval is taken as an indication that these therapies are safe . Our research efforts have led to three IND approvals of Phase 1/2 gene therapy clinical trials … Continued The ability to accurately determine the dose of an adeno-associated viral (AAV) therapeutic vector is critical to the gene therapy process. Another critical quality attribute for AAV-based gene therapy products is the empty/full capsids ratio, which is traditionally measured using density-based analytical centrifugation. Overview of AAV purification process 10:00 Process Development Approaches for AAV Gene Therapy Products. By Benjamin Boettner. Clearly, the use of AAV vectors in in-vivo gene therapy presents many advantages; they provide stable transgene in a variety of tissue types as well as being minimally pathogenic. Considerations for Preclinical Safety Assessment of Adeno-Associated Virus Gene Therapy Products Toxicol Pathol. . As we enhance our understanding of AAV . . TECARTUS (brexucabtagene autoleucel) Kite Pharma, Inc. YESCARTA (axicabtagene ciloleucel) Kite Pharma, Incorporated. Specific challenges of scaling up AAV production and considerations to accommodate a range of demands of differing gene therapy products will be discussed. What gene therapy developers desperately need is a production platform that can produce viral vectors . Fine-tune your AAV vector manufacturing. The aim of this study was to analyze the influence of the . single-stranded DNA. Introduction. 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