Kovalev Maxim A, Mamaeva Naida Yu, Kristovskiy Nikolay V, Feskin Pavel G, Vinnikov Renat S, Oleinikov Pavel D, Sosnovtseva Anastasiia O, Yakovlev Valeriy A, Glukhov Grigory S, Shaytan Alexey K
Department of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
Department of Fundamental Physical and Chemical Engineering, Lomonosov Moscow State University, 119234 Moscow, Russia.
Int J Mol Sci. 2025 Jul 2;26(13):6371. doi: 10.3390/ijms26136371.
Epigenome engineering, particularly utilizing CRISPR/dCas-based systems, is a powerful strategy to modulate gene expression and genome functioning without altering the DNA sequence. In this review we summarized current achievements and prospects in dCas-mediated epigenome editing, primarily focusing on its applications in biomedicine, but also providing a wider context for its applications in biotechnology. The diversity of CRISPR/dCas architectures is outlined, recent innovations in the design of epigenetic editors and delivery methods are highlighted, and the therapeutic potential across a wide range of diseases, including hereditary, neurodegenerative, and metabolic disorders, is examined. Opportunities for the application of dCas-based tools in animal, agricultural, and industrial biotechnology are also discussed. Despite substantial progress, challenges, such as delivery efficiency, specificity, stability of induced epigenetic modifications, and clinical translation, are emphasized. Future directions aimed at enhancing the efficacy, safety, and practical applicability of epigenome engineering technologies are proposed.
表观基因组工程，特别是利用基于CRISPR/dCas的系统，是一种在不改变DNA序列的情况下调节基因表达和基因组功能的强大策略。在本综述中，我们总结了dCas介导的表观基因组编辑的当前成就和前景，主要关注其在生物医学中的应用，但也为其在生物技术中的应用提供了更广泛的背景。概述了CRISPR/dCas结构的多样性，强调了表观遗传编辑器设计和递送方法的最新创新，并研究了其在包括遗传性、神经退行性和代谢性疾病在内的多种疾病中的治疗潜力。还讨论了基于dCas的工具在动物、农业和工业生物技术中的应用机会。尽管取得了重大进展，但仍强调了一些挑战，如递送效率、特异性、诱导表观遗传修饰的稳定性以及临床转化。提出了旨在提高表观基因组工程技术的疗效、安全性和实际适用性的未来方向。
