Organoids are 3D structures derived from stem cells that recapitulate key architectural and functional aspects of the corresponding tissue. Compared with conventional 2D cell lines, human organoids provide experimental models that more closely reflect human physiology. Their ability to capture the complexity and heterogeneity of human tissues enables the study of disease mechanisms, drug efficacy and toxicity. When generated from patient material, organoids also allow the assessment of individual drug responses. In this Review, we explore the utility of organoids in drug discovery. We outline current methodologies for generating and maintaining organoids, examine their applications in disease modelling, drug screening and safety evaluation, and consider regulatory aspects and the challenges for their broader adoption in drug discovery.

Dysregulated gene expression is associated with nearly all human disease and can be mediated by epigenetic modifications. Epigenetic editing aims to reprogramme gene expression by rewriting epigenetic signatures, without editing of the genome. Coined just over a decade ago, epigenetic editing initially faced major concerns regarding efficacy and specificity. Moreover, straightforward guidelines on how to induce sustained expression modulation for any given gene are still largely lacking. Yet, successes have been demonstrated in animal models of various diseases, and the first clinical trials of epigenetic editing have been initiated. Increased understanding of the mechanisms of epigenetic reprogramming is overcoming obstacles that initially hampered widespread application of epigenetic editing. Future advances in target specificity, reprogramming maintenance and delivery methods will enable epigenetic editing to become a powerful new therapeutic approach.