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原核生物的免疫系统:在基因编辑中的潜在应用及意义。

The immune system of prokaryotes: potential applications and implications for gene editing.

机构信息

School of Life Sciences, Chongqing University, Chongqing, China.

出版信息

Biotechnol J. 2024 Feb;19(2):e2300352. doi: 10.1002/biot.202300352.

Abstract

Gene therapy has revolutionized the treatment of genetic diseases. Spearheading this revolution are sophisticated genome editing methods such as TALENs, ZFNs, and CRISPR-Cas, which trace their origins back to prokaryotic immune systems. Prokaryotes have developed various antiviral defense systems to combat viral attacks and the invasion of genetic elements. The comprehension of these defense mechanisms has paved the way for the development of indispensable tools in molecular biology. Among them, restriction endonuclease originates from the innate immune system of bacteria. The CRISPR-Cas system, a widely applied genome editing technology, is derived from the prokaryotic adaptive immune system. Single-base editing is a precise editing tool based on CRISPR-Cas system that involves deamination of target base. It is worth noting that prokaryotes possess deamination enzymes as part of their defense arsenal over foreign genetic material. Furthermore, prokaryotic Argonauts (pAgo) proteins, also function in anti-phage defense, play an important role in complementing the CRISPR-Cas system by addressing certain limitations it may have. Recent studies have also shed light on the significance of Retron, a reverse transcription transposon previously showed potential in genome editing, has also come to light in the realm of prokaryotic immunity. These noteworthy findings highlight the importance of studying prokaryotic immune system for advancing genome editing techniques. Here, both the origin of prokaryotic immunity underlying aforementioned genome editing tools, and potential applications of deaminase, pAgo protein and reverse transcriptase in genome editing among prokaryotes were introduced, thus emphasizing the fundamental mechanism and significance of prokaryotic immunity.

摘要

基因治疗已经彻底改变了遗传性疾病的治疗方式。引领这场革命的是复杂的基因组编辑方法,如 TALENs、ZFNs 和 CRISPR-Cas,它们的起源可以追溯到原核生物的免疫系统。原核生物已经发展出各种抗病毒防御系统来对抗病毒攻击和遗传元件的入侵。对这些防御机制的理解为分子生物学中不可或缺的工具的发展铺平了道路。其中,限制酶来源于细菌的先天免疫系统。CRISPR-Cas 系统是一种广泛应用的基因组编辑技术,它源自原核生物的适应性免疫系统。单碱基编辑是一种基于 CRISPR-Cas 系统的精确编辑工具,涉及靶碱基的脱氨作用。值得注意的是,原核生物拥有脱氨酶作为其防御外来遗传物质的武器库的一部分。此外,原核 Argonaut (pAgo)蛋白也在抗噬菌体防御中发挥作用,通过解决 CRISPR-Cas 系统可能存在的某些限制,在补充 CRISPR-Cas 系统方面发挥着重要作用。最近的研究还揭示了 Retron 的重要性,Retron 是一种逆转录转座子,以前在基因组编辑中显示出潜力,在原核生物免疫中也开始显现。这些值得注意的发现强调了研究原核生物免疫系统对于推进基因组编辑技术的重要性。在这里,介绍了上述基因组编辑工具所基于的原核免疫的起源,以及脱氨酶、pAgo 蛋白和逆转录酶在原核生物基因组编辑中的潜在应用,从而强调了原核免疫的基本机制和意义。

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