TALE: a tale of genome editing.
TALE: a tale of genome editing.
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DOI：
10.1016/j.pbiomolbio.2013.11.006
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发表时间：
2014
影响因子：
3.8
通讯作者：
Mingjie Zhang;Feng Wang;Shi-Chang Li;Yan Wang;Yun Bai;Xue-qing Xu
中科院分区：
文献类型：
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作者：
Mingjie Zhang;Feng Wang;Shi-Chang Li;Yan Wang;Yun Bai;Xue-qing Xu
转录激活因子样效应子（TALE），首先在黄单胞菌属细菌中发现，是天然存在或人工设计的调节基因转录的蛋白质。这些蛋白质基于可变数目的串联重复序列识别并结合DNA序列。每个重复序列由一组约34个保守氨基酸组成;在该保守结构域内，通常有两个氨基酸将一个TALE与另一个TALE区分开。有趣的是，TALE揭示了一个简单的密码，用于一对一识别蛋白质的DNA碱基。合成TALE已被用于成功靶向包括人类在内的各种物种的基因。取决于融合到感兴趣的TALE的功能结构域的类型，这些蛋白质可以具有不同的生物学效应。例如，在结合DNA后，与转录激活结构域融合的TALE可以充当稳健转录因子（TALE-TF），而与限制性内切核酸酶（TALEN）融合的TALE可以切割DNA。理论上，靶向基因组编辑能够修饰任何感兴趣的内源性基因序列;这可以在细胞或生物体中进行，并可能在未来应用于临床基因治疗。以目前的技术，无法实现高度准确、特异和可靠的基因编辑。因此，TALE生物学的识别和结合机制是目前的研究热点。在这篇综述中，我们总结了TALE技术在过去几年中的主要进展，重点是TALE和DNA之间的相互作用，TALE的设计和构建，这种技术的潜在应用，以及使TALE上级锌指核酸内切酶的独特特性。
Transcription activator-like effectors (TALEs), first identified in Xanthomonas bacteria, are naturally occurring or artificially designed proteins that modulate gene transcription. These proteins recognize and bind DNA sequences based on a variable numbers of tandem repeats. Each repeat is comprised of a set of ∼34 conserved amino acids; within this conserved domain, there are usually two amino acids that distinguish one TALE from another. Interestingly, TALEs have revealed a simple cipher for the one-to-one recognition of proteins for DNA bases. Synthetic TALEs have been used to successfully target genes in a variety of species, including humans. Depending on the type of functional domain that is fused to the TALE of interest, these proteins can have diverse biological effects. For example, after binding DNA, TALEs fused to transcriptional activation domains can function as robust transcription factors (TALE-TFs), while fused to restriction endonucleases (TALENs) can cut DNA. Targeted genome editing, in theory, is capable of modifying any endogenous gene sequence of interest; this can be performed in cells or organisms, and may be applied to clinical gene-based therapies in the future. With current technologies, highly accurate, specific, and reliable gene editing cannot be achieved. Thus, recognition and binding mechanisms governing TALE biology are currently hot research areas. In this review, we summarize the major advances in TALE technology over the past several years with a focus on the interaction between TALEs and DNA, TALE design and construction, potential applications for this technology, and unique characteristics that make TALEs superior to zinc finger endonucleases.