Display of Self-Peptide on Adeno-Associated Virus Capsid Decreases Phagocytic Uptake in Vitro.

ABSTRACT: Adeno-associated virus (AAV) vectors are currently investigated as gene transfer agents for the treatment of a variety of diseases. However, activation of the host immune response upon vector administration limits the use of AAV in the clinical setting. To decrease host detection of AAVs, we tested the CD47-based "don't-eat-me" signal in the context of the AAV capsid. We genetically incorporated the bioactive region of CD47, named "self-peptide" (SP), onto the surface of the AAV2 capsid. AAV mutants were structurally and functionally characterized for vector production, SP and linker incorporation into the capsid, transduction efficiency, and phagocytic susceptibility. We demonstrate that utilizing linkers improves the AAV2 capsid's tolerance to SP insertion. Notably, the SP significantly

SUBMITTER: Robinson TM 

PROVIDER: S-EPMC9644873 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature