Therapeutic epigenome editing: safety and quality considerations of a new class of gene-targeted medicines

This focused insight article sheds light into the safety and quality-related aspects of an emerging class of gene-targeted epigenetic medicines based on target sequence specific genome-directed approaches. These combine with mechanisms using protein activators and suppressors of transcription and those affecting DNA methylation and histone modifications. Therapeutic modalities based on post-transcriptional mechanisms of gene regulation (such as siRNA) or non-specific epigenetic controls (such as histone deacetylase (HDAC) inhibitors) are outside the remit of this article. The ‘pros’ and ‘cons’ of targeted epigenetic therapies/epigenome editing relative to ‘standard’ gene therapy and genome editing approaches are discussed; and their prospects including the various therapeutic opportunities and current commercial development activities are illustrated. Emphasis on the additional safety considerations, which can be potentially unique to this therapeutic class, is also discussed. These considerations aim to de-risk the development of these novel modalities, and hence facilitate their transition into the clinic and beyond.