Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan; Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan.
Prog Mol Biol Transl Sci. 2024;208:185-209. doi: 10.1016/bs.pmbts.2024.07.003. Epub 2024 Aug 22.
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 方法彻底改变了基因编辑。表观遗传变化，包括 DNA 甲基化、RNA 修饰和组蛋白蛋白质的变化，已经得到了深入研究，并发现它们在人类疾病的发病机制中起着关键作用。虽然 DNA 和染色质修饰（称为表观遗传学）的用途已经得到很好的理解，但 RNA 核苷酸的各种改变的功能意义最近引起了关注。最近在改进基于 CRISPR 的表观遗传修饰方面的进展，为选择性修饰 DNA 的强大来源提供了可能，从而允许在多个细胞分裂中维持表观遗传记忆。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，因为 DNA 甲基化与这些疾病的发生和进展密切相关。遗传或表观遗传扰动会破坏印迹基因的调控，导致疾病的发生。当组蛋白密码编辑酶和 DNA 去/甲基转移酶与催化失活的 Cas9（dCas9）以及 CRISPRa 和 CRISPRi 结合使用时，它们在编辑真核细胞的表观基因组方面表现出优异的效果。因此，推进和优化细胞外递药平台可以进一步促进 CRISPR-Cas9 基因编辑技术在未来临床研究中的应用。本章重点介绍了 CRISPR/Cas9 系统如何为表观遗传修饰提供途径，以及它如何为人类带来益处。
