PT  - JOURNAL ARTICLE
AU  - Qin Huang
AU  - Ken Y. Chan
AU  - Isabelle G. Tobey
AU  - Yujia Alina Chan
AU  - Tim Poterba
AU  - Christine L. Boutros
AU  - Alejandro B. Balazs
AU  - Richard Daneman
AU  - Jonathan M. Bloom
AU  - Cotton Seed
AU  - Benjamin E. Deverman
TI  - Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP.B capsids
AID  - 10.1101/538421
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 538421
4099  - http://biorxiv.org/content/early/2019/02/01/538421.short
4100  - http://biorxiv.org/content/early/2019/02/01/538421.full
AB  - 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.