Attenuated and wild-type HIV-1 infections and long terminal repeat-mediated gene expression from plasmids delivered by gene gun to human skin ex vivo and macaques in vivo

Abstract

Gene expression from HIV-based gene therapy vectors or live-attenuated HIV-1 vaccines requires RNA transcription supported by the HIV-1 promoter, the long terminal repeat (LTR). Delivery of live-attenuated HIV-1 vaccines as plasmid DNA would overcome problems associated with production of attenuated HIV-1 strains. We investigated the expression of reporter plasmids and proviral HIV-1 constructs driven by either the HIV-1 LTR or LTRs with deletions in the U3 enhancer regions. LTR-driven plasmids were inoculated by gene gun into both human epidermis ex vivo and macaques in vivo. The HIV-1 LTR drove reporter gene expression in human and macaque skin, although with 15- to 20-fold less efficiency..