Context-Specific Function of the Engineered Peptide Domain of PHP.B
Recchia Martino, Edwin C. Fluck, Jacqueline Murphy, Qiang Wang, Henry Hoff, Ruth A. Pumroy, Claudia Y. Lee, Joshua J. Sims, Soumitra Roy, Vera Y. Moiseenkova‐Bell, James M. Wilson
Abstract
Targeting AAV vectors to specific cellular receptors is a promising strategy for enhancing expression in target cells or tissues while reducing off-target transgene expression. The AAV9-PHP.B/Ly6a interaction provides a model system with a robust biological readout that can be interrogated to better understand the biology of AAV vectors' interactions with target receptors. In this work, we analyzed the sequence and structural features required to successfully transfer the Ly6a receptor-binding epitope from AAV9-PHP.B to another capsid of clinical interest, AAV1. We found that AAV1- and AAV9-based vectors targeted to the same receptor exhibited different brain-transduction profiles. Our work suggests that, in addition to attachment-receptor binding, the capsid context in which this binding occurs is important for a vector's performance.