NONVIRAL AND VIRAL DELIVERY OF A HUMAN-IMMUNODEFICIENCY-VIRUS PROTECTIVE GENE INTO PRIMARY HUMAN T-CELLS

Because AIDS has been refractory to traditional pharmacologic interven tions, alternative approaches have been developed. Although the introd uction of specific antiviral genes into T leukemia cells can provide r elative 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, a gainst cloned and primary HIV isolates in human peripheral blood lymph ocytes and describe different methods of gene transfer into peripheral blood lymphocytes from HIV-infected individuals. We show that gold mi croparticles 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 deliv ery of HIV protective genes will facilitate the development of gene th erapy for AIDS and the analysis of viral and cellular gene expression in human T lymphocytes.