Expression of a protective gene prolongs survival of T cells in human immunodeficiency virus-infected patients

Clive Woffendin, Udaykumar Ranga, Zhi Yong Yang, Ling Xu, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

Abstract

The resistance of acquired immunodeficiency syndrome (AIDS) to traditional drug therapy has prompted a search for alternative treatments for this disease. One potential approach is to provide genetic resistance to viral replication to prolong latency. This strategy requires the definition of effective antiviral genes that extend the survival of T cells in human immunodeficiency virus (HIV)-infected individuals. We report the results of a human study designed to determine whether a genetic intervention can prolong the survival of T cells in HIV-infected individuals. Gene transfer was performed in enriched CD4+ cells with plasmid expression vectors encoding an inhibitory Rev protein, Rev M10, or a deletion mutant control, ΔRev M10, delivered by gold microparticles. Autologous cells separately transfected with each of the vectors were returned to each patient, and toxicity, gene expression, and survival of genetically modified cells were assessed. Cells that expressed Rev M10 were more resistant to HIV infection than those with ΔRev M10 in vitro. In HIV-infected subjects, Rev M10-transduced cells showed preferential survival compared to ΔRev M10 controls. Rev M10 can therefore act as a specific intracellular inhibitor that can prolong T-cell survival in HIV-1-infected individuals and potentially serve as a molecular genetic intervention which can contribute to the treatment of AIDS.

Original languageEnglish (US)
Pages (from-to)2889-2894
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number7
DOIs
StatePublished - Apr 2 1996
Externally publishedYes

Keywords

  • biolistics
  • gene therapy
  • Rev
  • transdominant

ASJC Scopus subject areas

  • Genetics
  • General

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