Targeted Myostatin Gene Editing in Multiple Mammalian Species Directed by a Single Pair of TALE Nucleases.
Targeted Myostatin Gene Editing in Multiple Mammalian Species Directed by a Single Pair of TALE Nucleases.
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DOI：
10.1038/mtna.2013.39
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发表时间：
2013-07-30
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肌肉生长抑制素 (MSTN) 是骨骼肌质量的负调节剂。人们广泛采用阻断肌生长抑制素信号通路的策略来增加包括肌营养不良症在内的各种疾病中的肌肉质量。在这里，我们报告了一类基于转录激活剂样效应核酸酶（TALEN）的新型试剂，可在基因组水平上破坏肌肉生长抑制素的表达。我们设计了一对 MSTN TALEN 以靶向肌肉生长抑制素基因编码区中高度保守的序列。我们证明，这些 MSTN TALEN 的共传递可在多种人类、牛和小鼠细胞中诱导高度特异性和有效的基因破坏。根据序列分析，这对 TALEN 预计在许多其他哺乳动物物种中发挥功能。此外，我们证明这些 MSTN TALEN 可以促进 mCherry 表达盒或较大的肌营养不良基因 (dysferlin) 表达盒定向整合到小鼠或人类细胞的 MSTN 基因座中。因此，使用我们高度特异性和高效的 TALEN 对对肌肉生长抑制素基因进行靶向编辑将促进细胞工程，从而有可能用于基于细胞的治疗的转化研究。
Myostatin (MSTN) is a negative regulator of skeletal muscle mass. Strategies to block myostatin signaling pathway have been extensively pursued to increase muscle mass in various disease settings including muscular dystrophy. Here, we report a new class of reagents based on transcription activator-like effector nucleases (TALENs) to disrupt myostatin expression at the genome level. We designed a pair of MSTN TALENs to target a highly conserved sequence in the coding region of the myostatin gene. We demonstrate that codelivery of these MSTN TALENs induce highly specific and efficient gene disruption in a variety of human, cattle, and mouse cells. Based upon sequence analysis, this pair of TALENs is expected to be functional in many other mammalian species. Moreover, we demonstrate that these MSTN TALENs can facilitate targeted integration of a mCherry expression cassette or a larger muscular dystrophy gene (dysferlin) expression cassette into the MSTN locus in mouse or human cells. Therefore, targeted editing of the myostatin gene using our highly specific and efficient TALEN pair would facilitate cell engineering, allowing potential use in translational research for cell-based therapy.
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影响因子：
56.9
作者：
Boch, Jens;Scholze, Heidi;Bonas, Ulla
通讯作者：
Bonas, Ulla
影响因子：
4
作者：
Menconi, Michael;Gonnella, Patricia;Petkova, Victoria;Lecker, Stewart;Hasselgren, Per-Olof
通讯作者：
Hasselgren, Per-Olof
影响因子：
4.5
作者：
Mosher DS;Quignon P;Bustamante CD;Sutter NB;Mellersh CS;Parker HG;Ostrander EA
通讯作者：
Ostrander EA
影响因子：
14.9
作者：
Doyle EL;Booher NJ;Standage DS;Voytas DF;Brendel VP;Vandyk JK;Bogdanove AJ
通讯作者：
Bogdanove AJ
影响因子：
64.8
作者：
通讯作者：
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