January 27th, 2024 - A briefing document from the FDA for the Cellular, Tissue, and Gene Therapies Advisory Committee Meeting entitled, “Toxicity Risks of Adeno-associated Virus (AAV) Vectors for Gene Therapy” (September 2021), recognizes the importance of incorporating NxGEN’s Transformative Technology into AAV vectors to evade the immune system for durable transgene expression.

The contribution of CpG dinucleotides in the vector genome in activating the innate immune mechanisms upon cellular entry is first mentioned on page 14 of the briefing. Section 2.4.2 goes into more detail on TLR9-dependent immune induction and recommends “codon modification to remove CpGs” as a strategy to circumvent CpG-mediated immune activation (page 16). 

Click here to read the Briefing Document