Efficient transduction of cytotoxic and anti-HIV-1 genes by a gene-regulatable lentiviral vector

摘要: Lentiviral vectors modified from human immunodeficiency virus type 1 (HIV-1) offer a promising approach for gene therapy, facilitating transduction of genes into non-dividing cells both in vitro and vivo. When transducing cytotoxic or anti-HIV genes, however, the vector must avoid self-inhibition by transgene that can lead to disruption production infectious virions. In this study, we constructed two HIV-1-based lentiviral harboring mifepristone-inducible expression unit either forward reverse orientation with respect direction viral genomic RNA. The ability these transduce was evaluated. CD14 used as transgene, were produced systems. efficiently induced transduced following treatment mifepristone. However, higher level basal observed system absence contrast, high titers containing vesicular stomatitis M successfully generated using vector, but not vector. addition, when VPS4B-dominant negative mutant against HIV-1 budding cloned significant amounts obtained. Subsequent VPS4B resulted approximately 50% inhibition only presence Our study thus demonstrates incorporation mifepristone-regulatable makes advances toward development allows harmful genes.