Next-generation strategies for managing AAV pre-existing immunity: beyond standard companion diagnostics

“Should IdeS treatment become standard, the use of assays to detect pre-existing antibodies may shift toward verifying IgG cleavage to confirm an adequate dosing window.”Pre-existing immunity to AAV limits the safety and efficacy of intravenous gene therapies, necessitating robust companion diagnostics for patient selection. This paper reviews current NAb and TAb assay approaches, standardization efforts, and emerging strategies, including engineered capsids and IgG-cleaving enzymes, that aim to overcome immunity and inform future diagnostic development.