Single domain antibody-based vectors in the delivery of biologics across the blood-brain barrier: a review.

Biologics are a promising and effective method for the treatment of central nervous system (CNS) diseases. The blood-brain barrier (BBB) is a natural barrier for the delivery of biologics into the brain, which decreases the effective concentration of drugs in the CNS. A range of strategies has been explored to transport biologics across the BBB endothelium, typically via receptor-mediated transcytosis (RMT), which involving molecules for endogenous BBB receptors to be fused with biologics. This review emphasized a category of novel alternative RMT-targeting vectors: single domain antibodies (sdAb). SdAbs are a unique category of antibodies derived from naturally occurring heavy-chain-only antibodies. Herein, we describe their properties, mechanisms, modifications, and translational perspectives for their ability to transmigrate across the BBB in vitro and in vivo in detail.