ATVcisLALA

ATVcisLALA is a specialized Antibody Transport Vehicle (ATV) scaffold developed by Denali Therapeutics to facilitate the delivery of therapeutic antibodies across the blood-brain barrier (BBB). It consists of an engineered Fc domain modified to bind monovalently (in a "cis" configuration) to the transferrin receptor (TfR), which mediates receptor-mediated transcytosis into the central nervous system. The monovalent binding is specifically designed to avoid receptor clustering and subsequent lysosomal degradation, thereby maintaining TfR levels on the cell surface. The "LALA" designation refers to the L234A and L235A mutations in the Fc region, which silence effector functions by reducing binding to Fc gamma receptors, minimizing potential inflammatory responses or target cell depletion. This modular platform serves as a base for various CNS-targeted candidates, including TREM2 agonists and enzyme replacement therapies.

Other names

ATV-LALAAntibody Transport Vehicle cis LALA