Cotransduction of nondividing cells using lentiviral vectors
Cotransduction of nondividing cells using lentiviral vectors
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DOI：
10.1038/sj.gt.3301283
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发表时间：
2000-09-01
期刊：
影响因子：
5.1
通讯作者：
Spector, SA
中科院分区：
文献类型：
--
作者：
Frimpong, K;Spector, SA
艾滋病和癌症等疾病可能需要将多个基因引入干细胞或非分裂细胞中，以达到治疗目的。这些基因可能在疾病途径的不同点起作用，或者可能构成一个调节环，以绕过或纠正支持疾病的缺陷基因或途径。理想的是，治疗性基因必须以不同的组合一起转导，并且导入应该不受限制地进行。由于慢病毒载体可以转导分裂和非分裂细胞，因此它们是研究组合基因转移到不同细胞中的理想载体。在这项研究中，我们证明，通过使用两个独立的慢病毒载体，假型与水泡性口炎病毒的蛋白g，多达四个基因可以同时引入到单个分裂和非分裂细胞。高达45%和73%的分裂和非分裂细胞，分别可以用两种慢病毒载体转导。共转导单个细胞的效率是单个转导效率的产物，表明不存在病毒干扰。使用慢病毒载体的多重和组合基因转导可能在基因治疗中被证明是有用的。
Diseases such as AIDS and cancers may require the introduction of multiple genes into either stem cells or nondividing cells, among others, for therapeutic purposes. Such genes may act at different points of the disease pathway or may constitute a regulatory loop to bypass or rectify the defective gene or pathway underpinning the disease. ideally, the therapeutic genes must be transduced together in diverse combinations, and the introduction should occur without constraints. Since lentiviral vectors can transduce both dividing and nondividing cells, they are ideal vehicles to investigate combinatorial gene transfer into diverse cells. In this study, we demonstrate that by using two independent lentiviral vectors, pseudotyped with the protein g of vesicular stomatitis virus, up to four genes can be introduced simultaneously into single dividing and nondividing cells. Up to 45% and 73% of dividing and nondividing cells, respectively, could be transduced with two lentiviral vectors. The efficiency of cotransducing a single cell was the product of the individual transduction efficiencies and suggested the absence of viral interference. Multiple and combinatorial gene transduction using lentiviral vectors may prove useful in gene therapy.