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.

Automated summary

Biologics are promising for treating central nervous system diseases, but the blood-brain barrier limits their delivery to the brain. Scientists have explored various strategies, such as receptor-mediated transcytosis, to overcome this limitation, with single domain antibodies emerging as a novel alternative targeting vector.