CRISPR–Cas13 systems use single-subunit RNA-guided Cas13 effectors for targeted RNA recognition and cleavage. This Review summarizes the recent advances in understanding the structural and mechanistic aspects of Cas13 systems and the diverse applications of these systems in biotechnology and therapeutics.

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.

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.

Oxybipins were identified as potent selective inhibitors of oxysterol-binding protein, promoting Golgi fragmentation, inhibiting retrograde trafficking and attenuating Shiga toxin toxicity.

Chemical, genetic and proteomic approaches were used to elucidate the mode of action of orpinolide, a withanolide-inspired OSBP inhibitor, revealing sterol transport as a druggable metabolic dependency in leukemia.

An efficient computational pipeline starting from validated peptide assemblies has been used to design two families of α-helical barrel proteins with functionalizable channels. This rationally seeded computational protein design approach delivers soluble, monomeric proteins that match the design targets accurately and with high success rates.

A tryptophan metabolite was identified that acts systemically to promote defense against bacterial infection by targeting kainate receptors (KARs), revealing a novel intersection between tryptophan metabolism and KARs in immune defense.

Biological nitrogen fixation requires low-potential electrons from ferredoxin or flavodoxin. Here the authors show how the soil diazotroph Azotobacter vinelandii employs the NADH:ferredoxin oxidoreductase RNF1 complex to lower the midpoint potential of the electron from NADH to reduce ferredoxin.

A photochromic dimerizer was developed for light-controlled reversible and quantitative regulation of intracellular protein localization, enabling optical control of PTEN-induced kinase 1 (PINK1)–Parkin-mediated mitophage induction.

The inaugural CRISPR-based drug Casgevy has been approved by several medical agencies, with other CRISPR-based therapies currently in clinical trials. Although there are technological hurdles to overcome, chemical biology has a vital role in developing recent breakthroughs in base editing, prime editing and epigenetic editing into future treatments.