NEWSROOM

Click here to view GEN Magazine, Cell and Gene Therapy Supplement

Click here to review the power point presentation Dr. Susan Faust presented at ASGCT.

A recent publication in Molecular Therapy detailed the data from eight gene therapy clinical trials, including variables such as the AAV serotype employed, the CpG dinucleotide content in the open reading frame of the therapeutic gene, the vector production method, the vector dosage and estimated total capsid dose, the immunosuppressive drugs administered, the correlation of AAV gene transfer with a cytotoxic T lymphocyte response (CTL) response, the outcome peak of the therapeutic transgene, and the durability of the transgene. The power of this clinical trial information is that it is the single largest AAV vector clinical data set for a single disease AAV gene therapy for hemophilia B—and allowed researchers to gain a clear insight into the key determinant for clinical success. Among the variables, CpG content was revealed to be the only factor that correlates well with clinical outcome and long-term transgene expression, with unmethylated CpG content in AAV vectors being the key attribute that triggers transgene expression-limiting immune responses in humans.
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NxGEN Vector Solutions merged last month with ImmunoCurex, a gene therapy company focused on generating programmed death ligand 1 (PD-L1) polypeptides for AAV gene transfer. NxGEN Vector Solutions will gain a second AAV gene therapy platform—an immunosuppressive therapy to treat immune or inflammatory diseases or conditions—and plans to continue to develop the technology. NxGEN Vector Solutions is collaborating with Robert Jarvik, MD, the inventor of the artificial heart and founder of Jarvik Heart, and Douglas McCarty, PhD, senior director of vector development at Pfizer, on this platform.
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The title of the abstract is CpG-Motifs within AAV Vectors Trigger Immune Activation upon Hepatic Gene Transfer. The results demonstrate that CpG depletion of AAV vector genomes provide an avenue to improve the clinical outcome of AAV-mediated gene transfer by preventing elimination of transgene product expressing hepatocytes by vector-induced T cell responses.

Dr. Faust will present in the symposium entitled Evolution of AAVs for Widespread Gene Delivery to the Central Nervous System. The title of her presentation is The Immune Response to CNS-Directed AAV Gene Therapy

Millions of patients worldwide suffer from diseases and disorders that can be cured with gene therapy: using viruses to introduce new, healthy, genes into the cells of patients.

The challenge lies in the fact that the body views new genes introduced by viruses as potential threats, and the body’s immune system fights off the viruses with the healthy genes.

NxGEN Vector Solutions Transformative Technology solves this problem.

Find out more at our reception.

Open Bar, Hors d’oeuvres, and Catered Buffet
Signature cocktail: “End of the Interferon”

CEO & Founder, Dr. Susan Faust, meets with ASGCT attendees to discuss NxGEN Vector Solutions’ Transformative Technology at the NxGEN Vector Solutions’ Exhibit Booth in 2019.

“The best trade-off one can currently imagine is to engineer rAAV vectors with better transduction efficiency, carrying optimized therapeutic transgenes and with reduced immunogenic profiles (CpG depleted genome, [Faust et al.], inert capsids, contaminant-free batches, minimum amounts of empty capsids, etc.). Such vectors would provide a higher therapeutic index, as they would permit therapeutic efficiency at doses sufficient to bypass pre-existing humoral immunity, but not high enough to trigger deleterious cellular immunity.”
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“It is important to develop suitable strategies to overcome vector directed immune responses. In this regard, CpG-depleted AAV vectors have been shown to evade immune detection [Faust et al.]. In their pioneering studies, Faust et al. initially tested the immunogenicity of AAVrh32.33 in wild type as well as Tlr9 knockout mice. They found that in Tlr9-deficient mice, IFNγ T cell responses toward capsid and transgene antigen were suppressed resulting in minimal cellular infiltrate and stable transgene expression.”
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