Why the study?
To guide the application of AAV-PHP.B vectors across disease models and inspire translational vectors for neurological diseases in humans, the host factors responsible for their central nervous system tropism needed to be elucidated.
Identifies LY6A as the essential receptor for AAV-PHP.B vectors, providing a mechanism for their enhanced CNS tropism and guiding future translational gene therapy development.
Mouse host factors for AAV-PHP.B CNS tropism identified; leaves open human vector translation.
The engineered AAV-PHP.B family of adeno-associated virus efficiently delivers genes throughout the mouse central nervous system. To guide their application across disease models, and to inspire the development of translational gene therapy vectors useful for targeting neurological diseases in humans, we sought to elucidate the host factors responsible for the CNS tropism of AAV-PHP.B vectors. Leveraging CNS tropism differences across mouse strains, we conducted a genome-wide association study, and rapidly identified and verified LY6A as an essential receptor for the AAV-PHP.B vectors in brain endothelial cells. Importantly, this newly discovered mode of AAV binding and transduction is independent of other known AAV receptors and can be imported into different cell types to confer enhanced transduction by the AAV-PHP.B vectors.
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Huang et al. (2019) studied this question.
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