Volume 23 Issue 5, May 2024

ADAR-based editors that can change the mRNA code offer new opportunities in both rare genetic diseases and common complex ones.

Since the groundbreaking discovery of RNAi more than 25 years ago, several small interfering RNA (siRNA)-based therapies that target the liver have gained approval. This Review discusses principal considerations in siRNA-based drug development, focusing on the medicinal chemistry of siRNA design, the application of informatics, delivery platforms and future directions.

The development of prodrugs — derivatives of active pharmaceutical ingredients (APIs) with little or no biological activity themselves that are converted into the API after administration — can address issues with properties of the API such as poor bioavailability. This article provides a holistic analysis of approved prodrugs and discusses trends in prodrug design, their indications, mechanisms of API release and the chemistry of promoieties added to APIs to form prodrugs.

Treatments for tuberculosis have markedly improved in recent years, but lung disease caused by nontuberculous mycobacteria (NTM) is on the rise and lacks effective cures. This Review discusses promising small-molecule drug candidates and innovative clinical trial designs and highlights how lessons from tuberculosis therapeutic development can be applied to NTM disease.