Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Hum Gene Ther. 2009 May;20(5):519-23. doi: 10.1089/hum.2008.170.
Foamy viral vectors and lentiviral vectors are attractive gene transfer vectors for hematopoietic stem cell gene therapy because they both efficiently transduce stem cells using rapid ex vivo transduction protocols designed to maintain engraftment potential. Here we directly compared the ability of foamy and lentiviral vectors to transduce long-term hematopoietic repopulating cells in the dog model, using a competitive repopulation assay with vectors that express enhanced yellow or green fluorescent proteins (EY/GFP). Mobilized canine peripheral blood CD34(+) cells were divided into two fractions and exposed to either foamy (EGFP) or lentiviral (EYFP) vectors at a multiplicity of infection of 5 in an 18-hr transduction protocol and then reinfused after conditioning with 920 cGy of total body irradiation. Both dogs studied had rapid neutrophil engraftment and multilineage engraftment of transduced cells. Marking was similar for both vectors, particularly at later time points, indicating that both vector types transduce long-term repopulating cells at similar frequencies.
泡沫状病毒载体和慢病毒载体是用于造血干细胞基因治疗的有吸引力的基因转移载体，因为它们都可以通过专门设计的快速体外转导方案有效地转导干细胞，以保持植入潜力。在这里，我们使用表达增强型黄色或绿色荧光蛋白 (EY/GFP) 的载体进行竞争重编程测定，直接比较了泡沫状和慢病毒载体在犬模型中转导长期造血重编程细胞的能力。将动员的犬外周血 CD34(+)细胞分成两部分，并在感染复数为 5 的情况下分别暴露于泡沫状 (EGFP) 或慢病毒 (EYFP) 载体中 18 小时的转导方案，然后在用 920cGy 全身照射进行调理后再输注。研究中的两只狗都有快速的中性粒细胞植入和转导细胞的多谱系植入。两种载体的标记相似，尤其是在后期时间点，表明两种载体类型以相似的频率转导长期重编程细胞。
