Integrated computational and experimental immunoengineering of adeno-associated virus capsid T cell epitopes in mice - PubMed
11 hours ago
- #gene therapy
- #AAV vectors
- #immunoengineering
- Adeno-associated virus (AAV) vectors are widely used in gene therapy but face immunogenicity challenges.
- The study combines computational prediction and experimental validation to engineer AAV9 capsids with reduced immunogenicity.
- The Epitope Modification and MHC Prediction (EMMP) pipeline was developed to evaluate amino acid substitutions for their effects on MHC presentability.
- Two mutant variants, R312H and R312Q, were evaluated, with R312Q showing reduced T-cell activation and anti-AAV9 antibody production.
- R312Q exhibited a slight reduction in transduction efficiency at low multiplicities of infection (MOI).
- The approach demonstrates potential for improving the safety and efficacy of AAV-based gene therapy.