Clinical promise aside, AAV capsids face challenges due to pre-existing NAb from individuals with prior exposure to wild-type AAV. These antibodies bind to viral capsids, impacting AAV-mediated gene transfer and diminishing gene therapy efficacy.
Addressing the presence of NAb during the development of AAV-based therapy, it is crucial to develop strategies to overcome capsid immunity. Strategies like epitope masking, directed evolution, plasmapheresis, IgG-degrading enzymes, and structural modifications have been developed to address capsid immunity.
Strategies to overcome capsid immunity:
Accurate NAb measurement with the current AAV-luciferase gold standard method faces challenges due to various factors, including high variability in AAV production from one batch to another, complex incubation procedures that can lead to assay variations, the presence of empty capsids, and matrix effects that can falsely lower the NAb assay results and create false positives.
Therefore, it is essential to have reproducible and specific in vitro assays for each AAV variant or serotype.
Furthermore, cell-based assays are crucial since they provide a direct and accurate evaluation of neutralization activity for each AAV serotype or variant.
Introducing the iLite® AAV NAb platform which offers a robust solution to address the challenges in current NAb assessment methods. The platform offers several benefits, including:
Muhuri M, Maeda Y,et al. Overcoming innate immune barriers that impede AAV gene therapy vectors. J Clin Invest. 2021