ASGCT 2021 – VJRegenMed

HSC gene editing: current approaches and remaining challenges

admin_vjr_user — Thu, 19 Aug 2021 11:17:13 +0000

Valentina Vavassori, PhD, IRCCS San Raffaele Scientific Institute & Vita-Salute San Raffaele University, Milan, Italy, provides an overview of the current landscape for hematopoietic stem cell (HSC) gene editing and describes key gene editing approaches used including the non-homologous end joining (NHEJ) and homology-directed repair (HDR) pathways. Key lines of ongoing research to advance HSC gene editing approaches include the improvement of HDR efficiency in HSCs, as well as the development of new tools, such as CRISPR-associated transposases, to circumvent toxicity associated with double-strand breaks. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

Enhancing AAV gene therapy in children with inborn errors of metabolism

admin_vjr_user — Wed, 18 Aug 2021 16:32:47 +0000

Gloria Gonzalez-Aseguinolaza, PhD, Universidad de Navarra, Pamplona, Spain & Vivet Therapeutics, Paris, France, explains that a key challenge associated with treating inborn errors of metabolism in children using non-integrating vector-based gene therapy is liver growth and therefore hepatocyte addition, which results in the dilution of therapeutic effect and need for re-administration. Subsequent doses are, however, typically less effective due to the presence of neutralizing antibodies following the first injection. Approaches being investigated to overcome this challenge include the use of ImmTOR tolerogenic nanoparticles carrying rapamycin which inhibit neutralising antibody formation, as well as strategies to reduce adeno-associated vector (AAV) genome loss during liver growth. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

Combining rAAV gene therapy with standard-of-care for the treatment of citrullinemia

admin_vjr_user — Wed, 18 Aug 2021 16:32:46 +0000

Gloria Gonzalez-Aseguinolaza, PhD, Universidad de Navarra, Pamplona, Spain & Vivet Therapeutics, Paris, France, discusses ongoing research into gene therapies for citrullinemia type I (CTLN1) in pediatric patients, a rare autosomal recessive genetic disorder caused by mutations in the ASS1 gene, that can result in early-onset hyperammonemia crisis. Combining standard of care nitrogen scavenger therapy with arginine administration prior to administration of VTX-804 gene therapy, a recombinant adeno-associated virus (rAAV) vector expressing the human ASS1 enzyme, has been demonstrated to control initial disease symptoms and improve therapeutic efficacy in a mouse model. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

Challenges in translating iPSC-based AMD therapies to the clinic

admin_vjr_user — Wed, 18 Aug 2021 16:32:45 +0000

Masayo Takahashi, MD, PhD, RIKEN Center for Biosystems Dynamics Research & Kobe City Eye Hospital, Kobe, Japan, discusses the challenges associated with the translation of induced pluripotent stem cell (iPSC)-based therapies to the clinic. She highlights the importance of developing robust culture protocols to help reduce lot-to-lot variation and explains that purity control of retinal pigment epithelium (RPE) cell products can be achieved based on pigmentation colour, which helps to avoid contamination. Another key challenge is the selection of suitable patients with age-related macular degeneration that will benefit from specific cell therapies. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

T cell and HSC gene editing for the treatment of Hyper-IgM Type 1

admin_vjr_user — Wed, 18 Aug 2021 16:32:44 +0000

Valentina Vavassori, PhD, IRCCS San Raffaele Scientific Institute & Vita-Salute San Raffaele University, Milan, Italy, describes a gene editing approach under investigation for the treatment of hyper IgM Type 1 (HIGM1), an immunodeficiency disorder caused by mutations in the gene for CD40L, a T-cell surface molecule. The strategy involves the insertion of a 5’-truncated corrective CD40L cDNA into the native gene, which restores gene function and maintains the physiological regulation of the gene. This editing strategy was applied to both autologous T cells and hematopoietic stem cells (HSCs), which were then transplanted into mouse models to compare therapeutic efficacy of the two cell types. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

HSC gene editing highlights from ASGCT 2021

admin_vjr_user — Wed, 18 Aug 2021 16:32:42 +0000

Valentina Vavassori, PhD, IRCCS San Raffaele Scientific Institute & Vita-Salute San Raffaele University, Milan, Italy, discusses her highlights from the American Society for Cell & Gene Therapy (ASGCT) Annual Meeting 2021. Exciting advances in gene editing technology include the development of CRISPR-associated transposase systems and prime editing, which can overcome toxicities associated with double-strand breaks in hematopoietic stem cells. In vivo genome editing is another promising area of research, despite safety and efficacy challenges that still need to be addressed before this technology can be used in the clinic. Dr Vavassori also highlights ongoing research into the potential of adverse events and toxicity caused by genome editing, including chromothripsis and translocations, as gene therapies approach clinical approval. This interview took place during the ASGCT 24th Annual Meeting 2021.

The potential of oncolytic adenoviral vectors

admin_vjr_user — Mon, 16 Aug 2021 08:50:48 +0000

Margarita Romanenko, PhD, University of Minnesota, Minneapolis, MN, discusses potential future applications of oncolytic adenoviral vectors. Currently approved vector-based COVID-19 vaccines utilize adenoviral vector technology of varying serotypes, including adenovirus serotype 6 (Ad6). Dr Romanenko anticipates that therapeutics based on a range of adenovirus serotypes will be developed in the future and highlights this technology’s promise given the oncolytic potential and capacity for gene insertion associated with oncolytic adenoviral vectors. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

Vector-based therapies for metabolic disorders

admin_vjr_user — Mon, 16 Aug 2021 08:50:47 +0000

Gloria Gonzalez-Aseguinolaza, PhD, Universidad de Navarra, Pamplona, Spain & Vivet Therapeutics, Paris, France, explains that the delivery of non-viral vectors containing small interfering RNAs (siRNAs), which inhibit toxic metabolite production, are an effective treatment option for inborn errors of metabolism such as acute intermittent porphyria. Alternative strategies include viral vector mediated gene therapy using adeno-associated vectors (AAVs), however vector transduction efficiency and gene integration must be improved to effectively treat inborn errors of metabolism. Other challenges associated with AAVs include inflammatory responses to high vector doses and exclusion of participants with anti-AAV antibodies. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

miCAR: combining microRNA gene silencing with CAR expression

admin_vjr_user — Fri, 13 Aug 2021 17:10:41 +0000

Marco Alessandrini, PhD, Antion Biosciences SA, Geneva, Switzerland, provides an overview of Therapeutic MiniGen (TMG) technology, a synthetic microRNA-based multiplex gene silencing technology for the engineering of allogeneic chimeric antigen receptor (CAR) T-cells. He also describes miCAR technology, a biomodal gene construct combining the TMG microRNA cassette with CAR expression, thus allowing the simultaneous silencing of multiple genes and expression of therapeutic proteins. This platform has allowed the generation of allogeneic miCAR T-cells specifically designed to overcome the immunosuppressive tumor microenvironment and achieve improved safety and efficacy. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

Developing CAR T-cell therapy for HIV

admin_vjr_user — Fri, 13 Aug 2021 17:10:39 +0000

Marco Alessandrini, PhD, Antion Biosciences SA, Geneva, Switzerland, discusses the development of an allogeneic chimeric antigen receptor (CAR) T-cell therapy for HIV. Antion’s novel miCAR platform was used to generate a bimodal gene construct that expressed both an HIV-specific CAR with a truncated CD4 receptor and a microRNA-based gene silencing cassette to silence CCR5, the T-cell receptor and inhibitory receptors, in order to enhance CAR T-cell persistence. This work highlights the potential to develop a scalable, cost-effective platform for creating off-the-shelf, universally accessible CAR-T therapy for HIV. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.