Induced pluripotent stem cells (iPSCs) provide a unique platform for individualized cell therapy approaches. Currently, episomal DNA, mRNA, and Sendai virus-based RNA reprogramming systems are widely used to generate iPSCs. However, they all rely on the use of multiple (three to six) components (vectors/plasmids/mRNAs) leading to the production of partially reprogrammed cells, reducing the efficiency of the systems. We produced a one-cycle measles virus (MV) vector by substituting the viral attachment protein gene with the green fluorescent protein (GFP) gene. Here, we present a highly efficient multi-transgene delivery system based on a vaccine strain of MV, a non-integrating RNA virus that has a long-standing safety record in humans. Introduction of the four reprogramming factors OCT4, SOX2, KLF4, and cMYC via a single, "one-cycle" MV vector efficiently reprogrammed human somatic cells into iPSCs, whereas MV vector genomes are rapidly eliminated in derived iPSCs. Our MV vector system offers a new reprogramming platform for genomic modification-free iPSCs amenable for clinical translation.

中文翻译：

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麻疹载体作为促进iPSC重编程的多基因递送平台。

诱导多能干细胞（iPSC）为个性化细胞治疗方法提供了独特的平台。当前，基于游离DNA，mRNA和仙台病毒的RNA重编程系统已广泛用于生成iPSC。但是，它们都依赖于使用多个（三到六个）成分（载体/质粒/ mRNA），导致产生部分重编程的细胞，从而降低了系统效率。我们用绿色荧光蛋白（GFP）基因取代了病毒附着蛋白基因，产生了一个单周期的麻疹病毒（MV）载体。在这里，我们介绍了一种基于MV疫苗株的高效多转基因递送系统，该疫苗株是一种非整合RNA病毒，在人类中具有长期的安全记录。通过一个“一个周期”引入四个重编程因子OCT4，SOX2，KLF4和cMYC MV载体有效地将人体细胞重编程为iPSC，而MV载体基因组在衍生的iPSC中迅速消除。我们的MV载体系统为适用于临床翻译的无需基因组修饰的iPSC提供了新的重编程平台。