Efficient lentiviral transduction of liver requires cell cycling in vivo.
Human-immunodeficiency-virus (HIV)-based lentiviral vectors are a promising tool for in vivo gene therapy. Unlike Moloney-murine-leukaemia-based retroviruses (MLV), lentiviruses are believed to stably transduce quiescent (non-cycling) cells in various organs. No previous studies, however, have directly established the cell-cycle status of any transduced cell type at the time of vector administration in vivo. In vitro studies using wild-type HIV or HIV-based vectors have shown that, in some cases, cell-cycle activation is required for infection, even though cellular mitosis is not an absolute requirement for integration. Even if the block in reverse transcription is overcome in quiescent T cells, productive infection by HIV cannot be rescued in the absence of cell-cycle activation. The potential use of these vectors for gene therapy prompted our study, which establishes a cell-cycle requirement for efficient transduction of hepatocytes in vivo.
Park
F
F
Department of Pediatrics, Stanford University, Stanford, California, USA.
Ohashi
K
K
Chiu
W
W
Naldini
L
L
Kay
M A
MA
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D051381:Rats; D011916:Rats, Inbred F344; D014161:Transduction, Genetic