Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; JST-ERATO, Japan.
Curr Opin Chem Biol. 2018 Oct;46:10-17. doi: 10.1016/j.cbpa.2018.03.011. Epub 2018 Apr 6.
In recent years, our knowledge of the epigenetic functions regulated by post-translational modifications (PTMs) of histones, and their role in various diseases, has expanded rapidly, opening the way to novel therapeutic strategies that treat epigenetic abnormalities. Many of the current approaches have been focusing on the chemical inhibition of histone-modifying enzymes to modulate histone PTM states for attaining therapeutic effects. However, recent developments in chemistry and molecular biology have contributed to the emergence of new methods that introduce histone PTMs entirely through artificial means, without reliance on endogenous enzymes. In this review article, we summarize several state-of-the-art approaches for the introduction of synthetic epigenetic modifications in cells, and discuss both their therapeutic potential and the possible challenges in developing novel therapeutic strategies utilizing them.
近年来,我们对组蛋白翻译后修饰(PTMs)调控的表观遗传功能及其在各种疾病中的作用的了解迅速扩展,为治疗表观遗传异常的新型治疗策略开辟了道路。目前的许多方法都集中在化学抑制组蛋白修饰酶上,以调节组蛋白 PTM 状态以达到治疗效果。然而,化学和分子生物学的最新发展促成了新方法的出现,这些方法完全通过人工手段引入组蛋白 PTM,而不依赖于内源性酶。在这篇综述文章中,我们总结了几种在细胞中引入合成表观遗传修饰的最新方法,并讨论了它们的治疗潜力和利用它们开发新的治疗策略可能面临的挑战。