The blood-brain barrier (BBB) limits entry of large molecule biologics into the brain. We generated heavy chain-only (HcAb) and common light chain antibodies against CD98hc as BBB shuttles via receptor-mediated transcytosis. These CD98-targeting shuttles significantly increased brain exposure, superior to that of benchmark antibodies and with excellent drug developability. These anti-CD98 shuttles are promising vectors for delivering biologic therapeutics to the central nervous system (CNS).
