A Single Surface-Exposed Amino Acid Determines Differential Neutralization of AAV1 and AAV6 by Human Alpha-Defensins.

ABSTRACT: Adeno-associated viruses (AAVs) are being developed as gene therapy vectors due to their low pathogenicity and tissue tropism properties. However, the efficacy of these vectors is impeded by interactions with the host immune system. One potential immune barrier to vector transduction is innate immune host defense peptides, such as alpha-defensins, which are potent antiviral agents against other nonenveloped viruses. To investigate the interaction between AAVs and alpha-defensins, we utilized two closely related AAV serotypes, AAV1 and AAV6. Although their capsids differ by only six residues, these two serotypes exhibit markedly different tissue tropisms and transduction efficiencies. Using two abundant human alpha-defensins, enteric human defensin 5 (HD5) and myeloid human neutrophil pepti

SUBMITTER: Porter JM 

PROVIDER: S-EPMC10062168 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature