Zachary Fitzpatrick

TL;DR: AAV8 vectors administered to mice passively immunized with anti-AAV8 BAbs showed a more efficient liver transduction and a unique vector biodistribution profile compared to mice immunizing with NAbs, highlighting a virtually opposite effect of neutralizing and binding antibodies on AAV vectors transduction.

TL;DR: It is demonstrated that in mice, AAV vectors associated with extracellular vesicles (EVs) can evade human anti-AAV neutralizing antibodies and it is shown that expressing a brain targeting peptide on the EV surface allowed significant enhancement of transduction compared to untargeted ev- AAV.

TL;DR: It is demonstrated that simple pelleting of exo-AAV from media via ultracentrifugation results in high-titer vector preparations capable of efficient transduction of central nervous system (CNS) cells after systemic injection in mice, and the ability of exosomes to evade neutralizing antibodies while still transducing CNS after peripheral delivery is clinically relevant.

TL;DR: The isolation of a novel CNS tropic AAV capsid, AAV-B1, after a single round of in vivo selection from an AAV Capsid library is reported, which represents an important improvement over AAV9 for CNS gene therapy.