Roth Goldie V, Gengaro Isabella R, Qi Lei S
Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
Department of Chemical Engineering, Stanford University, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Cell Chem Biol. 2024 Aug 6. doi: 10.1016/j.chembiol.2024.07.007.
The epigenome is a complex framework through which gene expression is precisely and flexibly modulated to incorporate heritable memory and responses to environmental stimuli. It governs diverse cellular processes, including cell fate, disease, and aging. The need to understand this system and precisely control gene expression outputs for therapeutic purposes has precipitated the development of a diverse set of epigenetic editing tools. Here, we review the existing toolbox for targeted epigenetic editing, technical considerations of the current technologies, and opportunities for future development. We describe applications of therapeutic epigenetic editing and their potential for treating disease, with a discussion of ongoing delivery challenges that impede certain clinical interventions, particularly in the brain. With simultaneous advancements in available engineering tools and appropriate delivery technologies, we predict that epigenetic editing will increasingly cement itself as a powerful approach for safely treating a wide range of disorders in all tissues of the body.
表观基因组是一个复杂的框架，通过它基因表达被精确且灵活地调控，以纳入可遗传记忆和对环境刺激的反应。它掌控着多种细胞过程，包括细胞命运、疾病和衰老。出于治疗目的而理解这个系统并精确控制基因表达输出的需求，促使了一系列多样的表观遗传编辑工具的发展。在这里，我们回顾了用于靶向表观遗传编辑的现有工具盒、当前技术的技术考量以及未来发展的机遇。我们描述了治疗性表观遗传编辑的应用及其治疗疾病的潜力，同时讨论了阻碍某些临床干预（尤其是在大脑中的干预）的当前递送挑战。随着可用工程工具和适当递送技术的同步进步，我们预测表观遗传编辑将越来越稳固地成为一种安全治疗身体所有组织中广泛疾病的强大方法。
