The recent success of mRNA vaccines has boosted the prospects for the development of a new class of designer medicines based on mRNA. This Review discusses the multiple design parameters that need to be carefully considered to create highly effective mRNA medicines.

Inflammasomes are central instigators of the inflammatory response to infection and tissue damage and key regulators in diverse diseases. Here, the authors describe signalling mechanisms that regulate the NLRP3 inflammasome pathways and recent progress in the development of inhibitors and agonists that are advancing into the clinic.

Current regulation of T cell receptor (TCR)-based therapeutics may require repeated testing of patients for specific HLA alleles as well as companion diagnostics development, despite the invariant nature of the HLA genotype and availability of robust clinical HLA tests. This increases the burden on patients and the organizations developing these products. We propose regulatory flexibility to facilitate the development of and access to TCR-based therapeutics.

Synapses are crucial nodes for communication between neurons and are frequently damaged or dysfunctional in a range of neurodegenerative diseases. In their Review, Dejanovic, Sheng and Hanson outline the current understanding of pathological mechanisms operating at the synapse. They discuss several synapse-targeted approaches in preclinical and clinical development, which could be particularly valuable in combination with other therapeutic strategies.

Current regulation of T cell receptor (TCR)-based therapeutics may require repeated testing of patients for specific HLA alleles as well as companion diagnostics development, despite the invariant nature of the HLA genotype and availability of robust clinical HLA tests. This increases the burden on patients and the organizations developing these products. We propose regulatory flexibility to facilitate the development of and access to TCR-based therapeutics.

Stuart Orkin, of Harvard Medical School and HHMI, discusses how the discovery of BCL11A paved the way for Vertex and CRISPR Therapeutics’ exa-cel therapy for haemoglobinopathies.