CRISPR-based genome editing has the potential to treat many human genetic diseases, but achieving stable, efficient and safe in vivo delivery remains a challenge. This Review assesses current delivery systems for genome editors—focusing on adeno-associated viruses and lipid nanoparticles—and highlights data from recent clinical trials. Emerging delivery systems and ongoing challenges in the field are discussed.

Merck & Co.’s PCSK9 inhibitor MK-0616 showcases the potential of macrocycles as oral drugs for extracellular targets, even as several companies explore intracellular and macrocycle–drug conjugate possibilities.

Advances in computational omics technologies are enabling access to the hidden diversity of natural products, and artificial intelligence approaches are facilitating key steps in harnessing the therapeutic potential of such compounds, including biological activity prediction. This article discusses synergies between these fields to effectively identify drug candidates from the plethora of molecules produced by nature, and how to address the challenges in realizing the potential of these synergies.

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.

ICER’s incoming President, Sarah Emond, discusses drug pricing, multimillion dollar gene therapies and innovation incentives.

Merck & Co.’s PCSK9 inhibitor MK-0616 showcases the potential of macrocycles as oral drugs for extracellular targets, even as several companies explore intracellular and macrocycle–drug conjugate possibilities.