Transfer of human artificial chromosome vectors into stem cells
Transfer of human artificial chromosome vectors into stem cells
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DOI：
10.1016/s1472-6483(10)60557-3
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Katoh, Motonobu
中科院分区：
文献类型：
--
作者：
Oshimura, Mitsuo;Katoh, Motonobu
人染色体片段和人人工染色体（HAC）是微细胞介导染色体转移的可行基因传递载体。构建HAC的策略包括“建立”或“自上而下”的方法。对于每种方法，都需要在供体细胞中操纵HAC以将HAC传递给受体细胞的技术。染色体片段或HAC与微细胞介导的染色体转移的结合促进了人类基因定位和各种遗传研究。近年来，以干细胞为基础的组织工程为基因和细胞治疗开辟了新的途径。现在的任务是开发安全有效的载体，将治疗性基因传递到特定的干细胞中，并维持这些基因的长期调控表达。虽然转移效率有待提高，但HAC具有基因治疗载体所需的几个特征，包括稳定的片段维持和大基因插入的能力。HAC也可以携带带有调控元件的基因组位点，这允许在类似于自然染色体的遗传环境中表达转基因。本文综述了近年来在胚胎干细胞和成体干细胞以及转基因动物中发展HAC和HAC介导的基因表达方面的研究成果和展望。
Human chromosome fragments and human artificial chromosomes (HAC) represent feasible gene delivery vectors via microcell-mediated chromosome transfer. Strategies to construct HAC involve either `build up' or `top-down' approaches. For each approach, techniques for manipulating HAC in donor cells in order to deliver HAC to recipient cells are required. The combination of chromosome fragments or HAC with microcell-mediated chromosome transfer has facilitated human gene mapping and various genetic studies. The recent emergence of stem cell-based tissue engineering has opened up new avenues for gene and cell therapies. The task now is to develop safe and effective vectors that can deliver therapeutic genes into specific stem cells and maintain long-term regulated expression of these genes. Although the transfer-efficiency needs to be improved, HAC possess several characteristics that are required for gene therapy vectors, including stable episomal maintenance and the capacity for large gene insets. HAC can also carry genomic loci with regulatory elements, which allow for the expression of transgenes in a genetic environment similar to the natural chromosome. This review describes the lessons and prospects learned, mainly from recent studies in developing HAC and HAC-mediated gene expression in embryonic and adult stem cells, and in transgenic animals.