A pathway from chromosome transfer to engineering resulting in human and mouse artificial chromosomes for a variety of applications to bio-medical challenges.
A pathway from chromosome transfer to engineering resulting in human and mouse artificial chromosomes for a variety of applications to bio-medical challenges.
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DOI：
10.1007/s10577-014-9459-z
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发表时间：
2015-02
影响因子：
2.6
通讯作者：
Inoue, Toshiaki
中科院分区：
文献类型：
--
作者：
Oshimura, Mitsuo;Uno, Narumi;Kazuki, Yasuhiro;Katoh, Motonobu;Inoue, Toshiaki
关键词：
微细胞介导的染色体转移（Microcell-mediated chromosome transfer，MMCT）是一种将特定供体细胞的染色体转移到受体细胞中，并将染色体作为基因传递载体的技术，为体细胞遗传学研究开辟了一条新的途径。然而，很难通过转移整个染色体或片段来揭示单个特定基因的功能，因为每个染色体或片段包含一组众多的基因。因此，替代工具是人人工染色体（HAC）和小鼠人工染色体（MAC）载体，其可以携带一个或多个感兴趣的基因。人道主义援助委员会/人道主义援助委员会主要是通过“自上而下的办法”（精心设计的创建）或“自下而上的办法”（重新创建）产生的。具有一个或多个受体位点的HAC/MAC表现出理想基因递送载体所需的几个特征，包括稳定的附加型维持和携带大基因组基因座及其调控元件的能力，从而允许以与天然染色体相似的方式对引入的基因进行生理调控。MMCT技术还用于操纵供体细胞中的HAC和MAC并将其递送至受体细胞。本文介绍了经验教训，并确定从研究中的HACs和MAC的建设，以及他们的能力，驱动外源基因表达在培养细胞和转基因动物通过MMCT的前景。还提出了生物医学挑战的各种应用的新途径。
Microcell-mediated chromosome transfer (MMCT) is a technique to transfer a chromosome from defined donor cells into recipient cells and to manipulate chromosomes as gene delivery vectors and open a new avenue in somatic cell genetics. However, it is difficult to uncover the function of a single specific gene via the transfer of an entire chromosome or fragment, because each chromosome or fragment contains a set of numerous genes. Thus, alternative tools are human artificial chromosome (HAC) and mouse artificial chromosome (MAC) vectors, which can carry a gene or genes of interest. HACs/MACs have been generated mainly by either a “top-down approach” (engineered creation) or a “bottom-up approach” (de novo creation). HACs/MACs with one or more acceptor sites exhibit several characteristics required by an ideal gene delivery vector, including stable episomal maintenance and the capacity to carry large genomic loci plus their regulatory elements, thus allowing the physiological regulation of the introduced gene in a manner similar to that of native chromosomes. The MMCT technique is also applied for manipulating HACs and MACs in donor cells and delivering them to recipient cells. This review describes the lessons learned and prospects identified from studies on the construction of HACs and MACs, and their ability to drive exogenous gene expression in cultured cells and transgenic animals via MMCT. New avenues for a variety of applications to bio-medical challenges are also proposed.
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DOI：
10.1038/nrg3116
发表时间：
2011-12-16
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Devoy A;Bunton-Stasyshyn RK;Tybulewicz VL;Smith AJ;Fisher EM
通讯作者：
Fisher EM
影响因子：
7.7
作者：
Grimes, BR;Schindelhauer, D;Cooke, HJ
通讯作者：
Cooke, HJ
通过将PHIC31积分酶和CRE重组酶的活性结合的大型和复杂转基因的体内组装。
影响因子：
14.9
作者：
Dafhnis-Calas, F;Xu, ZY;Haines, S;Malla, SK;Smith, MCM;Brown, WRA
通讯作者：
Brown, WRA
影响因子：
11.2
作者：
Anderson, BD;Nakamura, T;Peng, KW
通讯作者：
Peng, KW
影响因子：
3.5
作者：
BROWN, KE;BARNETT, MA;BROWN, WRA
通讯作者：
BROWN, WRA