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 efficien tly transducing CD4(+) cells. In order to increase the safety of this gene delivery system, we have now replaced the HIV-1 vector with an HI V-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 confer s Rev independence. The supernatant of psi 422 cells stably transfecte d with this new vector was capable of transducing CD4(+) cells with a titer of 10(4) transducing units per milliliter. This result shows tha t cross-packaging of HIV-2 vectors with the HIV-1 packaging cells is q uite 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 macrophag es, a key target cell in HIV infection; is an important advance in gen e therapy for AIDS.