AAV-mediated co-expression of an immunogenic transgene plus PD-L1 enables sustained expression through immunological evasion.

ABSTRACT: Adeno-associated virus (AAV) vectors can mediate long-term expression of immunogenic transgenes in vivo through transduction of tolerogenic cells in the liver. Tissue-targeted AAV vectors allow transduction of non-hepatic cells, but this necessitates development of strategies to minimize transgene immunogenicity. Here, we first validated that AAV capsids with tissue-specific tropism and transgene promoters enabled expression of the immunogenic protein, firefly luciferase, in liver, muscle, or adipose tissue. Cellular immunity was detectable in animals where luciferase was expressed in muscle or adipose, but not liver tissue. With the objective of enhancing tolerance of transduced non-hepatic cells, AAV vectors were engineered to co-express luciferase plus the immune checkpoint protein, PD-

SUBMITTER: McMurphy TB 

PROVIDER: S-EPMC11582688 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature