Transduction of human macrophages using a stable HIV-1/HIV-2-derived gene delivery system.
We have previously established a stable HIV-1 packaging cell line, psi 422, which yielded high titers of an HIV-1 vector capable of efficiently transducing CD4+ cells. In order to increase the safety of this gene delivery system, we have now replaced the HIV-1 vector with an HIV-2 vector to abolish any risk of homologous recombination between the packaging cells and the vector. The HIV-2 vector was also modified by insertion of a cis-acting constitutive transport element which confers Rev independence. The supernatant of psi 422 cells stably transfected with this new vector was capable of transducing CD4+ cells with a titer of 10(4) transducing units per milliliter. This result shows that cross-packaging of HIV-2 vectors with the HIV-1 packaging cells is quite efficient. Using this new stable HIV-1/HIV-2 gene delivery system, we were able to transduce human monocyte-derived primary macrophages, which are refractory to murine retrovirus-mediated transduction. The availability of a stable HIV-based gene delivery system for macrophages, a key target cell in HIV infection; is an important advance in gene therapy for AIDS.
Corbeau
P
P
Department of Medicine, University of California, San Diego, La Jolla 92093-0665, USA.
Kraus
G
G
Wong-Staal
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D015704:CD4 Antigens; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015497:HIV-1; D015498:HIV-2; D006801:Humans; D008264:Macrophages; D012190:Retroviridae; D014161:Transduction, Genetic; D019065:Virus Assembly
D015704:CD4 Antigens