Spleen necrosis virus-derived C-type retroviral vectors for gene transfer to quiescent cells

Gene therapy applications of retroviral vectors derived from C-type retrovi ruses have been limited to introducing genes into dividing target cells. He re, we report genetically engineered C-type retroviral vectors derived from spleen necrosis virus (SNV), which are capable of infecting nondividing ce lls, This has been achieved by introducing a nuclear localization signal (N LS) sequence into the matrix protein (MA) of SNV by site-directed mutagenes is. This increased the efficiency of infecting nondividing cells and was su fficient to endow the virus with the capability to efficiently infect growt h-arrested human T lymphocytes and quiescent primary monocyte-derived macro phages. We demonstrate that this vector actively penetrates the nucleus of a target cell, and has potential use as a gene therapy vector to transfer g enes into nondividing cells.