Rapid protection against human immunodeficiency virus type 1 (HIV-1) replication mediated by high efficiency non-retroviral delivery of genes interfering with HIV-1 tat and gag

Franco Lori, Julianna Lisziewicz, Jason Smythe, Andrea Cara, Tess A. Bunnag, David Curiel, Robert C. Gallo

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Efficient transduction of inhibitory genes is a critical requirement in the development of a gene therapy strategy against human immunodeficiency virus type 1 (HIV-1). Commonly used systems based on retrovirus-mediated gene delivery are characterized by low efficiency gene transfer into the target cell. Genes were transduced in the absence of cell selection into 60-90% of human CD4+ cells by using a novel technique that allows high efficiency gene transfer mediated by adenoviruses coupled with DNA-polylysine complexes. Protection of these cells against HIV-1 acute infection was evaluated by transducing them with three different inhibitory genes which interfere with HIV-1 replication at separate levels (polymeric Tat activation response element [TAR] decoy, dominant-negative mutant of the gag gene and antisense sequences of the gag gene) and subsequent challenging with HIV-1. The polymeric TAR decoy inhibited HIV-1 replication over 95%. Both the dominant-negative mutant and the antisense sequence of the gag gene were less potent inhibitors than the polymeric-TAR decoy. Combinations of either polymeric-TAR with dominant-negative mutant or antisense of the gag gene synergistically enhanced the inhibitory effects of the single genes. These data suggest that the combination of a highly efficient transduction technique with effective HIV-1 inhibitory genes confers rapid protection against HIV-1 acute infection in vitro.

Original languageEnglish
Pages (from-to)27-31
Number of pages5
JournalGene therapy
Volume1
Issue number1
StatePublished - Dec 1 1994

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