September 8th, 2021 - Dr. Susan Faust is an invited guest speaker presenting at the Gene Therapy Summit, Vector Engineering & Design, taking place in Boston, MA on Apr 12, 2022
1) Short Course: Capsid or Genome: What’s Causing the Transgene-Limiting Immune Response Following AAV Gene Transfer?
2) Podium Presentation: Adeno-Associated Virus (AAV) Gene Transfer of a Localized Immunosuppressant in Cardiac Transplants for the Prevention of Chronic Rejection
July 14th, 2021 - NxGEN Vector Solutions’ CEO, Dr. Susan Faust, is an invited guest speaker at the #VLGeneCellGene and Cell Therapies: CMC, CGT & Vector Manufacturing Summit
November 18-19, 2021| 9:00 CEST |Munich, Germany & Online
Dr. Faust will be speaking on:
The desirability of CpG depletion of AAV vectors for the purpose of reducing the immune response to the vector and establishing long-term transgene expression
The mechanism by which immunostimulatory CpG motifs limit transgene expression (presenting data from both preclinical and clinical studies) as well as strategies for the future design of AAV vectors
May 24th, 2021 - NxGEN Vector Solutions Announces Issuance of a New U.S. Patent Covering CpG-depleted AAV Vector Technology
May 25th, 2021—NxGEN Vector Solutions announces today that the U.S. Patent and Trademark Office has issued a new Patent, No. 11,015,210, further strengthening the Company’s intellectual property position and coverage for the Company’s CpG-depletion AAV Vector Technology.
The ‘210 patent, entitled, “Constructs and Methods for Delivering Molecules via Viral Vectors with Blunted Innate Immune Responses,” covers a modified recombinant adeno-associated viral vector to reduce the number of CpG di-nucleotides such that an immune response to the vector is reduced.
There are four independent claims and they are drawn to various AAV vector compositions in which the regulatory sequence and the exogenous sequence of the AAV vector is CpG-reduced or CpG-free and the AAV ITRs are wild type or CpG-reduced. The regulatory sequence can be a promoter, an enhancer, an intron, a microRNA, or a polyA signal sequence.
The issued patent demonstrates NxGEN Vector Solutions’ commitment to developing innovative therapies that improve AAV gene therapy outcome by establishing persistent transgene expression, evading immunity, and minimizing infiltration of effector cells. We are pleased with the issuance of the patent and excited about the potential of this technology–which is already being used in clinical trials and has quickly become an industry standard–to improve the safety and efficacy of gene therapies and to ensure that patients who receive gene therapy maintain their therapeutic gene expression.
April 20th, 2021 - 2021—Read the original CpG-depletion AAV vector technology scientific article, Faust et al., JCI, 2013. We were the first to develop and demonstrate that CpG-depleted AAV vectors could establish persistent transgene expression, evade immunity, and minimize infiltration of effector cells. We concluded and accurately predicted that CpG-depleted AAV vectors could improve outcome of clinical trials of gene therapy.
March 18th, 2021 - March 18, 2021–NxGEN Vector Solutions’ CEO, Dr. Susan Faust, is an invited guest speaker at the Vector Engineering & Delivery for Gene Therapies summit to take place on April 20, 2021. Additional information on the presentation can be found below:
Title: Hindsight is 2020: The Advancement of CpG-depleted AAV Vectors as an Industry Standard
The desirability of CpG depletion of AAV vectors for the purpose of reducing the immune response to the vector and establishing long-term transgene expression is a hot topic in the manufacturing sector and of interest to many gene therapists. Dr. Faust is a pioneer in this research and the first to CpG-deplete AAV vectors to circumvent TLR9 activation, a technology that has become an industry standard.
The audience will gain an in depth understanding of the mechanism by which immunostimulatory CpG motifs limit transgene expression (presenting data from both preclinical and clinical studies) as well as strategies for the future design of AAV vectors.
February 14th, 2021 - February 14, 2021—An editorial published in Blood by Lindsey A. George, M.D. (Children’s Hospital of Philadelphia) entitled No CpGs for AAVs? comments on the human clinical trial, NCT01687608, which explored a self-complementing optimized AAV vector to deliver the human FIX-Padua gene (Konkle et al., 2019). The treatment, BAX335, also known as AskBio009, employed an increased number of CpG di-nucleotides (ie. from 19 to 99) in the FIX open reading frame. Ultimately, the results of the clinical trial confirmed that long-term transgene expression was not achieved with AAV vectors having increased CpG content in the coding sequence for the transgene despite steroid intervention due to the innate immune stimulatory effect of CpG motifs enriched within their vector cassette.
November 19th, 2020 - November 19, 2020 – You’ve probably seen the plethora of papers and presentations in 2020 demonstrating that stable transgene expression in human clinical trials is dependent on the AAV vector genome CpG motifs. This confirms the preclinical studies performed nearly 8 years ago by Dr. Susan Faust and Dr. Joseph Rabinowitz–both members of NxGEN Vector Solutions–and pioneers of CpG-depleted AAV vectors (NxGEN Technology). The desirability of CpG depletion of AAV vectors for the purpose of reducing the immune response to the vector and establishing long-term transgene expression is very hot in the manufacturing sector and of great interest to gene therapists.
Dr. Paul Monahan has published a superb scientific article detailing the results of clinical trial NCT01687608 (Shire/Baxalta BAX335 aka Askbio009) for hemophilia B showing that long-term transgene expression was not achieved with AAV vectors having increased CpG content in the coding sequence for the transgene. Dr. Monahan concludes that BAX335 did not provide long-term expression of the FIX transgene in the clinical trial “due to the innate immune stimulatory effect of CpG motifs enriched within their vector cassette.” Through clinical data analysis, murine studies, and a retrospective on the field at the time of the launch of the BAX35 clinical trial, Dr. Monahan elegantly provides insights into the mechanism whereby CpG motifs result in transient transgene expression despite steroid administration in patients, with implications on the future design of AAV vectors.
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