In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector

A retroviral vector system based on the human immunodeficiency virus (HIV) was de-veloped that, in contrast to a murine leukemia virus-based counterpart, transduced heterologous sequences into HeLa cells and rat fibroblasts blocked in the cell cycle, as well as into human primary macrophages. Additionally, the HIV vector could mediate stable in vivo gene transfer into terminally differentiated neurons. The ability of HIV-based viral vectors to deliver genes in vivo into nondividing cells could increase the applicability of retroviral vectors in human gene therapy. Until now, gene therapy protocols have often relied on vectors derived from retro-viruses such as murine leukemia virus (MLV) (1, 2). These vectors are useful because the genes they transduce are inte-grated into the genome of the target cells, a desirable feature for long-term expression. However, these retroviral vectors can onl