伪互补肽核酸核酸酶(pcPNANs)能否成为基因工程的新工具

Penghui Shi
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引用次数: 0

摘要

锌指核酸酶(ZFNs)和转录激活因子样效应核酸酶(TALENs)构成了一类强大的工具,正在重新定义生物学研究的边界。尽管这些技术已经开始实现有针对性的基因组修饰,但仍然需要可扩展、负担得起且易于设计的新技术。本文提出了一种新的基因工程工具——伪互补肽核酸核酸酶(pcPNANs),它由DNA靶序列特异性的伪互补PNA (pcPNA)、FokI核酸酶切割结构域和核定位信号组成。pcPNANs可以诱导靶向DNA双链断裂,激活DNA损伤反应途径并实现自定义改变。它们的切割位点由简单的沃森-克里克规则确定,因此可以直接设计和合成用于基因组定向切割的pcPNANs,而不需要任何选择程序。因此,通过改变pcPNA链的序列和长度,可以自由选择裂解位点和位点特异性。我们相信pcPNAN作为基因工程新工具的潜力将在未来得到证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Can pseudocomplementary peptide nucleic acid nucleases (pcPNANs) be a new tool for genetic engineering
Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) comprise a powerful class of tools that are redefining the boundaries of biological research. Although these technologies have begun to enable targeted genome modifications, there remains a need for new technologies that are scalable, affordable, and easy to engineer. In this paper, we propose a new tool for genetic engineering, the pseudocomplementary peptide nucleic acid nucleases (pcPNANs), which are composed of a pseudocomplementary PNA (pcPNA) specific for a DNA target sequence, a FokI nuclease cleavage domain and a nuclear localization signal. pcPNANs may induce targeted DNA double-strand breaks that activate DNA damage response pathways and enable custom alterations. Their cleavage-site is determined by simple Watson-Crick rule, and thus pcPNANs for aimed cleavage of genomes can be straightforwardly designed and synthesized without any selection procedure. Accordingly, the cleavage-site and site-specificity are freely chosen by changing the sequences and the lengths of pcPNA strands. We believe that the potentiality of pcPNAN as a new tool for genetic engineering will be confirmed in the future.
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