{"title":"Advances in CRISPR-Cas systems for epigenetics.","authors":"Mahnoor Ilyas, Qasim Shah, Alvina Gul, Huzaifa Ibrahim, Rania Fatima, Mustafeez Mujtaba Babar, Jayakumar Rajadas","doi":"10.1016/bs.pmbts.2024.07.003","DOIUrl":null,"url":null,"abstract":"<p><p>The CRISPR-Cas9 method has revolutionized the gene editing. Epigenetic changes, including DNA methylation, RNA modification, and changes in histone proteins, have been intensively studied and found to play a key role in the pathogenesis of human diseases. CRISPR-While the utility of DNA and chromatin modifications, known as epigenetics, is well understood, the functional significance of various alterations of RNA nucleotides has recently gained attention. Recent advancements in improving CRISPR-based epigenetic modifications has resulted in the availability of a powerful source that can selectively modify DNA, allowing for the maintenance of epigenetic memory over several cell divisions. Accurate identification of DNA methylation at specific locations is crucial for the prompt detection of cancer and other diseases, as DNA methylation is strongly correlated to the onset as well as the advancement of such conditions. Genetic or epigenetic perturbations can disrupt the regulation of imprinted genes, resulting in the development of diseases. When histone code editors and DNA de-/ methyltransferases are coupled with catalytically inactive Cas9 (dCas9), and CRISPRa and CRISPRi, they demonstrate excellent efficacy in editing the epigenome of eukaryotic cells. Advancing and optimizing the extracellular delivery platform can, hence, further facilitate the manipulation of CRISPR-Cas9 gene editing technique in upcoming clinical studies. The current chapter focuses on how the CRISP/ Cas9 system provides an avenue for the epigenetic modifications and its employability for human benefit.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"208 ","pages":"185-209"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in molecular biology and translational science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.pmbts.2024.07.003","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
The CRISPR-Cas9 method has revolutionized the gene editing. Epigenetic changes, including DNA methylation, RNA modification, and changes in histone proteins, have been intensively studied and found to play a key role in the pathogenesis of human diseases. CRISPR-While the utility of DNA and chromatin modifications, known as epigenetics, is well understood, the functional significance of various alterations of RNA nucleotides has recently gained attention. Recent advancements in improving CRISPR-based epigenetic modifications has resulted in the availability of a powerful source that can selectively modify DNA, allowing for the maintenance of epigenetic memory over several cell divisions. Accurate identification of DNA methylation at specific locations is crucial for the prompt detection of cancer and other diseases, as DNA methylation is strongly correlated to the onset as well as the advancement of such conditions. Genetic or epigenetic perturbations can disrupt the regulation of imprinted genes, resulting in the development of diseases. When histone code editors and DNA de-/ methyltransferases are coupled with catalytically inactive Cas9 (dCas9), and CRISPRa and CRISPRi, they demonstrate excellent efficacy in editing the epigenome of eukaryotic cells. Advancing and optimizing the extracellular delivery platform can, hence, further facilitate the manipulation of CRISPR-Cas9 gene editing technique in upcoming clinical studies. The current chapter focuses on how the CRISP/ Cas9 system provides an avenue for the epigenetic modifications and its employability for human benefit.
CRISPR-Cas9 方法为基因编辑带来了革命性的变化。包括 DNA 甲基化、RNA 修饰和组蛋白变化在内的表观遗传学变化已被深入研究,并被发现在人类疾病的发病机制中起着关键作用。CRISPR--虽然 DNA 和染色质修饰(即表观遗传学)的作用已广为人知,但 RNA 核苷酸的各种改变的功能意义最近也受到了关注。最近,在改进基于 CRISPR 的表观遗传修饰方面取得了进展,从而提供了一种可以选择性修饰 DNA 的强大资源,使表观遗传记忆可以在多次细胞分裂中得以维持。由于 DNA 甲基化与癌症和其他疾病的发生和发展密切相关,因此准确识别特定位置的 DNA 甲基化对于及时发现癌症和其他疾病至关重要。遗传或表观遗传扰动会破坏印记基因的调控,导致疾病的发生。当组蛋白代码编辑器和 DNA 脱/甲基转移酶与无催化活性的 Cas9(dCas9)、CRISPRa 和 CRISPRi 相结合时,它们在编辑真核细胞的表观基因组方面表现出卓越的功效。因此,推进和优化细胞外递送平台可进一步促进 CRISPR-Cas9 基因编辑技术在即将开展的临床研究中的应用。本章将重点讨论 CRISP/ Cas9 系统如何为表观遗传修饰提供途径,以及它是否能造福人类。
期刊介绍:
Progress in Molecular Biology and Translational Science (PMBTS) provides in-depth reviews on topics of exceptional scientific importance. If today you read an Article or Letter in Nature or a Research Article or Report in Science reporting findings of exceptional importance, you likely will find comprehensive coverage of that research area in a future PMBTS volume.