Recent advances in structural biology techniques and computational simulations have enhanced our understanding of the conformational dynamics of G protein-coupled receptors and their interactions with ligands. This Review highlights how such advances may be used in the discovery and optimization of drugs that target G protein-coupled receptors, focusing on three categories: allosteric modulators, biased ligands, and bivalent and bitopic compounds.

CRISPR technology is revolutionizing the development of therapies for genetic disorders. However, the application of CRISPR-based therapeutics is challenged by factors impacting stability, efficiency, delivery and safety. This Review focuses on chemical engineering of CRISPR–Cas systems to address these issues, it assesses next-generation CRISPR–Cas systems, and it highlights CRISPR-based therapies that are approved or in clinical development.

Regulatory T cells keep the immune system in check to maintain homeostasis and restrain inflammation. This Review discusses strategies to harness these cells therapeutically for autoimmunity, transplant tolerance or cancer, for example, by boosting their endogenous function, depleting them or administering them as engineered cell-based therapies.

CD8 T cells and natural killer (NK) cells play a key role in cancer immunosurveillance. However, their anticancer activity is rapidly diminished in the tumour microenvironment, associated with a decline in their metabolic function. This Review provides an overview of metabolic programmes in CD8 T cells and NK cells, discusses the dysfunction that can occur in cancer, and assesses therapeutic strategies to overcome this.