Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities is now standard practice in pharmaceutical research and development. This article uses a survey across 18 companies as the basis for discussing strategies for implementing secondary pharmacology screening programmes, approaches for interpreting off-target activities and which targets to include in screening panels, including several targets not commonly included in existing panels.

‘Pre-mRNA trans-splicing’ drugs could offer an alternative to gene replacement therapies for genetic diseases — starting with Stargardt disease.

The rise of drug resistance presents a significant challenge in the treatment of infectious diseases. This Review summarizes the status and mechanisms of drug resistance in malaria, human immunodeficiency virus (HIV) infection and tuberculosis, and explores strategies to address resistance that could be incorporated into drug development across these disease areas.

RNA has revolutionized modern medicine, creating great expectations. However, challenges with this class of drugs persist. In this Review, John Androsavich analyses lessons learnt from RNA modalities such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNA), and discusses strategies to develop RNA drug platforms, improving their applicability, efficacy and safety profiles.

‘Pre-mRNA trans-splicing’ drugs could offer an alternative to gene replacement therapies for genetic diseases — starting with Stargardt disease.

The passage of the FDA Modernization Act 2.0 in 2022 has provided additional impetus to develop new approach methods for predicting the effects of drug candidates in humans from models such as microphysiological systems based on human-derived induced pluripotent stem cells. Here, we highlight progress in the field and strategies to address various challenges, including the application of artificial intelligence tools.