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Lentivirus vectors: difficulties and hopes before clinical trials.

The ability to transduce non-dividing cells is a unique feature of lentiviruses which distinguishes them from simple retroviruses. This feature was the major incentive for the development of the lentivirus vector system. Lentivirus vectors can deliver and integrate > 8 kb of transgenic DNA into target cell genomes without inducing a host immune response against the transduced cells. Thus lentivirus vector-based gene delivery can be considered the most efficient method by which transgenes can be incorporated into the host cell genome and maintain long-term expression. This review describes the major developments in the lentivirus vector system, which significantly improve vector biosafety, vector production and transgene expression. The success and difficulties in reverting disease phenotypes by lentivirus vectors carrying therapeutic genes in various animal models including beta-thalassemia and Parkinson's disease and the implications of these studies for future gene therapy clinical trials are also discussed.