This Review provides an overview of different RNA base editing technologies, including the RNA-targeting platforms and modification effectors, with a focus on the emerging programmable RNA base editors and their potential in correcting pathological mutations.

Chemical approaches, such as those that leverage induced proximity, targeted degradation, synthetic gene regulators or protein design offer opportunities to therapeutically target cellular processes that have long been thought of as undruggable. We report on the progress and the potential for transformative collaborations between fields discussed at the 2023 Bringing Chemistry to Medicine symposium at St. Jude Children’s Research Hospital.

AlphaFold is a breakthrough in protein structure prediction, but limitations in its application to computation- and structure-guided drug discovery remain. As with structure prediction, public-domain data and benchmarking initiatives will be essential to advance the field of computational drug design.

Sulfated compounds produced collaboratively by the microbiome and the host have important biological functions. This Review highlights the production of select sulfated carbohydrates, amino acid derivatives and steroidal metabolites and discusses their influence on health. The Review also explore potential roles of sulfated molecules in disease detection, prevention and treatment.

Zuo et al. developed a highly bright and stable green fluorescent RNA for robust imaging of the dynamics of messenger RNA in living cells, enabling visualization of nonuniform and distinct distributions of different RNAs throughout stress granules.

Engineered living materials harness the computational power of biology to control interesting material properties. Here the authors leverage complex transcriptional regulation of bacterial extracellular electron transfer to control hydrogel cross-linking with Boolean logic.

Owens et al. reported PFI-7, a selective and potent antagonist of GID4 of the CTLH E3 ligase complex, which enables identification of human GID4 targets. This study provides valuable insights into GID4 functions and a powerful tool for advancing new targeted protein degradation strategies.

Yin et al. discover that the phosphatase PTENα acts as an RNA-binding protein, mitigating viral-induced inflammation in the brain by constraining RIG-I activation, suggesting PTENα as a potential therapeutic target for viral infection.

A newly developed maternally selective nanobody antagonist against the angiotensin II type I receptor stabilizes the receptor in a hybrid conformation and simultaneously binds with specific small-molecule antagonists.

Biochemical pathways for aromatic amino acid synthesis are ancient and highly conserved. Directed evolution of the β-subunit of tryptophan synthase (TrpB)—a proficient biocatalyst that converts indole to l-tryptophan—enabled this enzyme to make l-tyrosines from phenols, a pathway not (yet) known in nature.