Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning.

ABSTRACT: Therapeutic payload delivery to the central nervous system (CNS) remains a major challenge in gene therapy. Recent studies using function-driven evolution of adeno-associated virus (AAV) vectors have successfully identified engineered capsids with improved blood-brain barrier (BBB) penetration and CNS tropism in mouse. However, these strategies require transgenic animals and thus are limited to rodents. To address this issue, we developed a directed evolution approach based on recovery of capsid library RNA transcribed from CNS-restricted promoters. This RNA-driven screen platform, termed TRACER (Tropism Redirection of AAV by Cell-type-specific Expression of RNA), was tested in the mouse with AAV9 peptide display libraries and showed rapid emergence of dominant sequences. Ten individual va

SUBMITTER: Nonnenmacher M 

PROVIDER: S-EPMC7841218 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature