Volume 22 Issue 10, October 2023

Merck & Co.’s PCSK9 inhibitor MK-0616 showcases the potential of macrocycles as oral drugs for extracellular targets, even as several companies explore intracellular and macrocycle–drug conjugate possibilities.

In vivo gene supplementation using adeno-associated virus (AAV) vectors holds substantial promise for a range of neurological disorders. In this Review, the authors discuss ongoing clinical trials and growing knowledge on factors that affect translational success and safety. They outline approaches to increase efficacy and reduce potential toxicity, including optimization of the AAV vector, and consider new frontiers and unmet needs in the field.

Malaria case numbers are rising globally and there is a vital need for new medicines that overcome the emergence of drug resistance. This Review describes the current landscape of small-molecule antimalarial therapies and the methods used to discover them as well as perspectives on approaches to find new targets and treatments.

Cytokines mediate a broad range of cellular functions, and the regulation of their activity is important both physiologically and pathologically. This Review explores the biology, signalling and regulation of cytokines and their receptors. Focusing on IL-2, engineering strategies and agents aimed at therapeutically redirecting and fine-tuning cytokine actions, particularly for applications in cancer and autoimmune disease, are assessed.