Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications

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.