Abstract: Disclosed herein are binding agents, conjugates, and extracellular vesicles that enhance penetration of the blood brain barrier. Uses thereof for delivery of agents, e.g., therapeutic agents, to the central nervous system are also provided.

Abstract: Disclosed herein are methods of delivering a polypeptide, e.g., an antibody or antigen binding portion thereof, to the central nervous system of a subject, by administering to the subject the polypeptide (e.g., antibody or antigen-binding portion thereof) conjugated to the surface of an extracellular vesicle (EV) derived from a neural cell, e.g., a neural progenitor cell or a neural stem cell. Conjugates comprising neural EVs coupled to a polypeptide, such as an antibody or antigen binding portion thereof, and methods of use thereof, are also provided. Also disclosed herein are methods of delivering a polypeptide, e.g., an antibody or antigen binding portion thereof, by administering to the subject the polypeptide (e.g., antibody or antigen-binding portion thereof) loaded within the lumen of an extracellular vesicle (EV) derived from neural cells.