Abstract
Because AIDS has been refractory to traditional pharmacologic interventions, alternative approaches have been developed. Although the introduction of specific antiviral genes into T leukemia cells can provide relative resistance to human immunodeficiency virus (HIV) replication, the testing of such genes against primary viral isolates in human CD4+ lymphocytes has been limited, and safety questions remain regarding gene delivery into cells from HIV-infected patients. In this report, we evaluate the efficacy of a transdominant mutant protein, Rev M10, against cloned and primary HIV isolates in human peripheral blood lymphocytes and describe different methods of gene transfer into peripheral blood lymphocytes from HIV-infected individuals. We show that gold microparticles can mediate stable Rev M10 gene transfer into these cells. Introduction of Rev M10 by these techniques conferred resistance to HIV infection in vitro to cloned and clinical isolates. Nonviral delivery of HIV protective genes will facilitate the development of gene therapy for AIDS and the analysis of viral and cellular gene expression in human T lymphocytes.
MeSH Terms
Base Sequence
Cells, Cultured
DNA Primers/chemistry
Gene Products, rev/administration & dosage
Gene Transfer Techniques
Genes, Dominant
Genes, Suppressor
Genes, rev
Genetic Therapy
Gold
HIV Infections/prevention & control
HIV-1/genetics
Humans
In Vitro Techniques
Molecular Sequence Data
T-Lymphocytes/microbiology
Transduction, Genetic
Transfection
Virus Replication
rev Gene Products, Human Immunodeficiency Virus
Chemicals
DNA Primers
Gene Products, rev
rev Gene Products, Human Immunodeficiency Virus
Gold
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Woffendin C
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor.
Yang Z Y
Udaykumar
Xu L
Yang N S
Sheehy M J
Nabel G J
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