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.

Click here to read the Editorial

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.

Click here to check out Dr. Monahan’s Blood publication.

October 6th, 2020 - October 6, 2020 — NxGEN Vector Solutions received trademark protection for the NxGEN logo.

NxGen Vector Solutions

September 8th, 2020 - September 8, 2020 – Partner with NxGEN Vector Solutions to apply NxGEN Technology to your AAV vectors and eliminate the immune response that limits transgene durability. Learn more in the May issue of Genetic Engineering & Biotechnology News (GEN Magazine) on pages 10-11.

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

April 12th, 2020 - April 12, 2020 – Wright, 2020. Codon Modification and PAMPs in Clinical AAV Vectors: The Tortoise or the Hare? Molecular Therapy, Vol. 28, No. 3.

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.
Click here for full article

March 1st, 2020 - March 1, 2020 – NxGEN Vector Solutions was featured in the March 2020 Issue of Genetic Engineering and Biotechnology News (GEN Magazine).

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.
Click here to read more.

February 14th, 2020 - February 14, 2020 – NxGEN Vector Solutions has submitted a scientific abstract to the 23rd Annual Meeting of American Society of Gene and Cellular Therapy, Boston, Massachusetts, May 12-15, 2020.

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.

December 11th, 2019 - December 11, 2019 – NxGEN Vector Solutions CEO, Dr. Susan Faust, is an invited guest speaker at the American Society of Experimental Neurotherapeutics Annual Meeting, which will take place March 2-5, 2020 in Bethesda, MD.

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