Retroviral vectors derived from lentiviruses such as HIV-1 are promisi
ng tools for human gene therapy because they mediate the in vivo deliv
ery and long-term expression of transgenes in nondividing tissues. We
describe an HIV vector system in which the virulence genes env, vif, v
pr, vpu, and nef have been deleted. This multiply attenuated vector co
nserved the ability to transduce growth-arrested cells and monocyte-de
rived macrophages in culture, and could efficiently deliver genes in v
ivo into adult neurons. These data demonstrate the potential of lentiv
iral vectors in human gene therapy.