Human Receptor 1 (at the blood-brain barrier) (Receptor 1)

Human Receptor 1 (at the blood-brain barrier) is a putative protein receptor identified by Sangamo Therapeutics as the primary mediator for the transport of the engineered AAV capsid STAC-BBB across the blood-brain barrier (BBB). This receptor is highly expressed on the luminal surface of brain endothelial cells and facilitates the entry of AAV vectors into the central nervous system (CNS) through receptor-mediated transcytosis (RMT). STAC-BBB binds to this receptor with high affinity, typically in the low picomolar range, which is significantly stronger than the binding of the parental AAV9 serotype. The interaction between STAC-BBB and Receptor 1 is conserved across humans, non-human primates, and mice, providing a robust mechanism for cross-species translation of gene therapies. This receptor is a critical target for the delivery of genomic medicines, including zinc finger epigenetic regulators, designed to treat devastating neurological conditions such as prion disease and tauopathies. By utilizing Receptor 1, STAC-BBB achieves widespread brain transduction and potent gene repression while minimizing off-target delivery to peripheral tissues like the liver.

Other names

Putative STAC-BBB receptorReceptor 1 (Sangamo)CNSRCV300 receptorBlood-brain barrier Receptor 1

Binding to Receptor 1 on the luminal surface of brain endothelial cells to facilitate receptor-mediated transcytosis (RMT) of AAV capsids across the blood-brain barrier.