Journal
MOLECULAR THERAPY
Volume 12, Issue 6, Pages 1206-1216Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2005.06.483
Keywords
gene transfer; lentiviral vector; quiescent cells; SIVsmmPBj; monocytes; chromosomal integration
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Despite the ability to infect non proliferating cells, current lentiviral vectors are inefficient at mediating gene transfer into quiescent primary human cells such as monocytes. Here, a replication-incompetent vector based on a molecular clone of simian immunodeficiency virus strain PBj (SIVsmmPBj1.9) was generated that, in contrast to lenti- and gamma-retroviral control vectors, enabled transfer of heterologous genes into human diploid fibroblasts and cell lines blocked in the Go phase of the cell cycle. Moreover, freshly isolated human monocytes refractory to HIV-1-derived vectors were efficiently transduced by the PBj vector independent of the viral Nef protein. Stable chromosomal integration of PBj-derived viral expression vectors was verified in transduced cells. The capability of the PBj vector to transduce quiescent cells such as unstimulated primary human monocytes is an important extension of human gene therapy perspectives.
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