Polymers Shepherd RNA Drugs

A new polymeric drug delivery system inspired by bacterial toxins could aid medical use of RNA drugs, which often get inactivated shortly after they are introduced into cells. Cationic polymers have been used as nucleic acid delivery vehicles for more than a decade, but many of them don’t work well enough for medical applications. After entering cells, the polymers and their payloads often get trapped within endosomes and lysosomes, where they are rendered inactive. Now, a team led by Patrick S. Stayton of the University of Washington, Seattle, has developed RNA-binding copolymer micelles with domains that are neutral or negatively charged under ambient conditions. At standard physiological pH, carboxylic acid groups in these polymers have a negative charge. Endosomes and lysosomes have acidic interiors that can protonate these groups. Once they have been protonated, the polymers adopt a new conformation that disrupts the structure of the compartments, releasing their cargo. The work “addresses one of the critical aspects of siRNA delivery,” said Peter D. Senter of Seattle Genetics, namely keeping drug molecules out of cell endosomes and lysosomes.