mRNA technology is being applied to develop a new generation of therapies for rare and common diseases. This Review discusses insights from clinical studies on mRNA-based therapeutics, including enzyme replacement therapies, cancer immunotherapies, genome-modifying therapies and immune cell reprogramming therapies, which illustrate how technological advances are paving the way for the wider adoption of mRNA technology in drug development.

Claudins are emerging as clinically actionable targets in cancer, exemplified by the approval of CLDN-18.2-directed therapy. This review examines the biological basis and therapeutic exploitation of claudins, highlighting diverse targeting modalities and the shift towards leveraging tight junction components as tumour-selective entry points for precision oncology strategies.

Agonistic antibodies initiate signalling by the receptors they target, mimicking the activities of native ligands. This Review discusses the clinical successes and failures of agonistic antibodies and explains how recent mechanistic insights should broaden the scope and improve the safety and efficacy of immunotherapies based on these agents.

Autophagy has a highly complex and context-dependent role in cancer, challenging the development of autophagy-modulating strategies. This Review discusses the potential of targeting autophagy to counteract malignant transformation, prevent disease progression and enable anticancer immunosurveillance. Existing and emerging pharmacological strategies and the associated limitations are critically presented.