Nonviral and viral delivery of a human immunodeficiency virus protective gene into primary human T cells.
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.
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor.
C
C
Woffendin
Z Y
ZY
Yang
Udaykumar
L
L
Xu
N S
NS
Yang
M J
MJ
Sheehy
G J
GJ
Nabel
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D015694:Gene Products, rev / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D005799:Genes, Dominant; D016153:Genes, Suppressor; D015757:Genes, rev; D015316:Genetic Therapy; D006046:Gold; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000382:microbiology*; D014161:Transduction, Genetic; D014162:Transfection; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D015694:Gene Products, rev; D054321:rev Gene Products, Human Immunodeficiency Virus; D006046:Gold