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Development of Sendai Virus Vectors and their Potential Applications in Gene Therapy and Regenerative Medicine

机译:仙台病毒载体的开发及其在基因治疗和再生医学中的潜在应用

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摘要

Gene delivery/expression vectors have been used as fundamental technologies in gene therapy since the 1980s. These technologies are also being applied in regenerative medicine as tools to reprogram cell genomes to a pluripotent state and to other cell lineages. Rapid progress in these new research areas and expectations for their translation into clinical applications have facilitated the development of more sophisticated gene delivery/expression technologies. Since its isolation in 1953 in Japan, Sendai virus (SeV) has been widely used as a research tool in cell biology and in industry, but the application of SeV as a recombinant viral vector has been investigated only recently. Recombinant SeV vectors have various unique characteristics, such as low pathogenicity, powerful capacity for gene expression and a wide host range. In addition, the cytoplasmic gene expression mediated by this vector is advantageous for applications, in that chromosomal integration of exogenous genes can be undesirable. In this review, we introduce a brief historical background on the development of recombinant SeV vectors and describe their current applications in gene therapy. We also describe the application of SeV vectors in advanced nuclear reprogramming and introduce a defective and persistent SeV vector (SeVdp) optimized for such reprogramming.
机译:自1980年代以来,基因递送/表达载体已被用作基因治疗的基本技术。这些技术也被用作再生医学的工具,以将细胞基因组重编程为多能状态和其他细胞谱系。这些新研究领域的飞速发展以及人们对其转化为临床应用的期望,促进了更复杂的基因递送/表达技术的发展。自从1953年在日本分离出仙台病毒(SeV)以来,它已广泛用作细胞生物学和工业研究工具,但直到最近才对SeV作为重组病毒载体的应用进行了研究。重组SeV载体具有多种独特特征,例如低致病性,强大的基因表达能力和广泛的宿主范围。另外,由该载体介导的细胞质基因表达对于应用是有利的,因为外源基因的染色体整合可能是不希望的。在这篇综述中,我们介绍了重组SeV载体开发的简要历史背景,并描述了它们在基因治疗中的当前应用。我们还描述了SeV向量在高级核重编程中的应用,并介绍了针对此类重编程优化的有缺陷且持久的SeV向量(SeVdp)。

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