Volume 23 Issue 2, February 2024

The FDA approved 55 novel therapeutics in 2023, the second highest count in the past 30 years.

The potential of harnessing tRNAs to treat genetic diseases has recently gained significant attention. Here, Coller and Ignatova provide an overview of the history and potential applications of tRNA-based therapies, summarize advances in tRNA cargo design and delivery strategies, and assess the challenges encountered in establishing tRNAs as effective and safe therapeutics.

A diverse range of systems have recently been developed to promote the degradation of extracellular and membrane protein targets by using bispecific antibodies, conjugates or small molecules to traffic targeted proteins to the lysosome. This article describes and categorizes systems for extracellular targeted protein degradation, including LYTACs, ATACs, AbTACs, PROTABs and KineTACs, and discusses their advantages and the challenges ahead to realizing their therapeutic potential.

Advances with deep learning, the growth of databases of molecules for virtual screening and improvements in computational power have supported the emergence of a new field of quantitative structure–activity relationship (QSAR) modelling applications that Tropsha et al. term ‘deep QSAR’. This article discusses key advances in the field, including deep generative and reinforcement learning approaches in molecular design, deep learning models for synthetic planning, and the use of deep QSAR models in structure-based virtual screening.