Abstract
Delivering large biologic drugs into the brain is severely hindered by the strict regulation of the blood-brain barrier (BBB). To overcome this obstacle, we engineered novel CD98hc-targeting antibodies—specifically, heavy-chain-only (HcAb) and common light-chain formats—designed to function as BBB shuttles utilizing receptor-mediated transcytosis. Our evaluations reveal that these CD98-directed vehicles achieve substantially higher brain penetration than current benchmark antibodies, while also maintaining highly favorable developability profiles. Consequently, these innovative anti-CD98 shuttles emerge as highly effective delivery platforms for transporting therapeutic biologics directly into the central nervous system (CNS).
