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CRISPR-Cas 在推进精准牙周病学中的作用。

The role of CRISPR-Cas in advancing precision periodontics.

机构信息

Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.

Michael G. DeGroote School of Medicine, McMaster University, Toronto, ON, Canada.

出版信息

J Periodontal Res. 2021 Jun;56(3):454-461. doi: 10.1111/jre.12846. Epub 2021 Jan 16.

Abstract

The significant advancement of molecular biology has revolutionized medicine and provided important technologies to further clinical research development. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are DNA sequences derived from bacteriophages which have previously infected the bacterial species. The CRISPR-Cas system plays a key role in bacterial defense by detecting and destroying DNA fragments during subsequent bacteriophage invasions. The Cas9 enzyme recognizes and cleaves new invading CRISPR-complementary DNA sequences. Researchers have taken advantage of this biological device to manipulate microbes' genes and develop novel therapeutics to tackle systemic disease. In this review, we discuss the potential of utilizing CRISPR-Cas systems in the periodontal field to develop personalized periodontal care. We summarize promising attempts to bring this technology to the clinical setting. Finally, we provide insights regarding future developments to best utilize the CRISPR-Cas systems to advance precision periodontics. Although further research is imperative to evaluate the safety and potential of using CRISPR-Cas to develop precision periodontics approaches, few studies showed promising data to support the investment into this important technology in the dental sector. CRISPR-Cas9 can be a useful tool to create knockouts in vitro and in vivo as a screening tool to identify cellular pathways involved in the pathogenesis of periodontitis. Alternative CRISPR systems such as CRISPRa, CRISPRi, and Cas13 can be used to modify the transcriptome and gene expression of genes involved in periodontitis progression. CRISPR systems such as Cas3 can be used to target the periodontal biofilm and to develop new strategies to reduce or eliminate periodontal pathogens. Currently, the utility of CRISPR-Cas applications in clinical settings is limited. Through this review, we hope to foster further discussion in the periodontal research and clinical communities with respect to the potential clinical application of novel, CRISPR-Cas based, therapeutics for periodontitis.

摘要

分子生物学的重大进展彻底改变了医学,为进一步的临床研究发展提供了重要技术。规律成簇间隔短回文重复(CRISPR)是先前感染细菌的噬菌体衍生的 DNA 序列。CRISPR-Cas 系统在细菌防御中起着关键作用,通过在随后的噬菌体入侵期间检测和破坏 DNA 片段。Cas9 酶识别并切割新入侵的与 CRISPR 互补的 DNA 序列。研究人员利用这种生物装置来操纵微生物的基因,并开发新的疗法来治疗系统性疾病。在这篇综述中,我们讨论了在牙周领域利用 CRISPR-Cas 系统开发个性化牙周护理的潜力。我们总结了将这项技术推向临床的有希望的尝试。最后,我们提供了关于未来发展的见解,以最好地利用 CRISPR-Cas 系统推进精密牙周学。虽然进一步的研究对于评估使用 CRISPR-Cas 开发精密牙周学方法的安全性和潜力至关重要,但少数研究提供了有希望的数据来支持在牙科领域投资这项重要技术。CRISPR-Cas9 可以作为一种有用的工具,在体外和体内创建基因敲除,作为一种筛选工具来识别参与牙周炎发病机制的细胞途径。替代的 CRISPR 系统,如 CRISPRa、CRISPRi 和 Cas13,可以用于修饰与牙周炎进展相关的基因的转录组和基因表达。CRISPR 系统,如 Cas3,可以用于靶向牙周生物膜,并开发新的策略来减少或消除牙周病原体。目前,CRISPR-Cas 应用在临床环境中的实用性有限。通过这篇综述,我们希望在牙周研究和临床社区中进一步讨论新型基于 CRISPR-Cas 的治疗牙周炎的潜在临床应用。

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