Articles in 2023

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.

Duchenne muscular dystrophy is an inherited muscle-wasting disease caused by mutations that disrupt production of dystrophin protein. This Review discusses the plethora of therapeutic approaches being developed to restore dystrophin function, such as exon skipping, gene replacement, cell therapy and gene editing, and highlights recent clinical approvals.

Despite major advances in cancer research, we are falling short in bringing innovative medicines to children with cancer. We propose a new business model to incentivize investors, private companies and public organizations to invest in drug development for paediatric cancers.

Vividion CEO Aleksandra Rizo discusses emerging lessons from the firm’s use of fragment-based screening — including the potential for allosteric covalent drugs to drive different functional effects through a single binding site.

Several forms of non-apoptotic cell death, such as necroptosis, pyroptosis, parthanatos and ferroptosis, are implicated in degenerative diseases, cancer and inflammation. This article describes the molecular pathways regulating these forms of cell death and gives an update on small-molecule inhibitors being developed to target these pathways.

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.

Innovative approaches to conducting proof-of-concept trials could accelerate the evaluation of repurposed drugs. Drawing lessons from repurposing efforts for COVID-19 therapies, here we present a vision for a drug repurposing platform that could maximize efficiency and improve patient outcomes for many different conditions.