Yamada K, Olsen J C, Patel M, Rao K W, Walsh C E
UNC Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Mol Ther. 2001 Apr;3(4):485-90. doi: 10.1006/mthe.2001.0287.
Lentiviral vectors transduce nondividing hematopoietic cells more efficiently than other currently available vector systems. Here we report the results of human hematopoietic cell gene transfer using lentiviral vectors based upon human immunodeficiency virus (HIV-1) and equine infectious anemia virus (EIAV). EIAV is a nonprimate lentivirus and is severely restricted in its host range to horses and closely related equines. We employed the EIAV vector system to test for gene transfer to human Fanconi anemia (FA) hematopoietic cells by comparison with HIV-1- and Moloney murine leukemia virus-based systems. Fanconi anemia is characterized by bone marrow failure secondary to stem cell dysfunction. Fanconi anemia group C EBV-transformed lymphoblasts were transduced with all three viral vectors. Phenotypic correction of FA cells, as measured by mitomycin C drug resistance, was observed with a similar efficiency in all vector systems. This is the first description of lentiviral correction of FA cells and suggests that lentiviral vectors may be useful for FA gene transfer.
慢病毒载体比目前其他可用的载体系统更有效地转导非分裂造血细胞。在此，我们报告了使用基于人类免疫缺陷病毒（HIV-1）和马传染性贫血病毒（EIAV）的慢病毒载体进行人类造血细胞基因转移的结果。EIAV是一种非灵长类慢病毒，其宿主范围严格限于马和与之密切相关的马科动物。我们采用EIAV载体系统，通过与基于HIV-1和莫洛尼鼠白血病病毒的系统进行比较，来测试向人类范可尼贫血（FA）造血细胞的基因转移。范可尼贫血的特征是继发于干细胞功能障碍的骨髓衰竭。用所有三种病毒载体转导范可尼贫血C组EB病毒转化的淋巴细胞。在所有载体系统中，通过丝裂霉素C耐药性测定，观察到FA细胞的表型校正效率相似。这是对FA细胞慢病毒校正的首次描述，并表明慢病毒载体可能对FA基因转移有用。
