Sutton R E, Wu H T, Rigg R, Böhnlein E, Brown P O
Department of Biochemistry and Howard Hughes Medical Institute, Stanford University Medical Center, Stanford, California 94305, USA.
J Virol. 1998 Jul;72(7):5781-8. doi: 10.1128/JVI.72.7.5781-5788.1998.
Lentiviruses are potentially advantageous compared to oncoretroviruses as gene transfer agents because they can infect nondividing cells. We demonstrate here that human immunodeficiency virus type 1 (HIV-1)-based vectors were highly efficient in transducing purified human hematopoietic stem cells. Transduction rates, measured by marker gene expression or by PCR of the integrated provirus, exceeded 50%, and transduction appeared to be independent of mitosis. Derivatives of HIV-1 were constructed to optimize the vector, and a deletion of most of Vif and Vpr was required to ensure the long-term persistence of transduced cells with relatively stable expression of the marker gene product. These results extend the utility of this lentivirus vector system.
与致癌逆转录病毒相比,慢病毒作为基因传递载体具有潜在优势,因为它们可以感染非分裂细胞。我们在此证明,基于人类免疫缺陷病毒1型(HIV-1)的载体在转导纯化的人类造血干细胞方面效率很高。通过标记基因表达或整合前病毒的PCR测量的转导率超过50%,并且转导似乎与有丝分裂无关。构建了HIV-1的衍生物以优化载体,并且需要删除大部分Vif和Vpr以确保转导细胞的长期存活以及标记基因产物的相对稳定表达。这些结果扩展了这种慢病毒载体系统的用途。