Rolling Circle Transcription of Tandem siRNA to Generate Spherulitic RNA Nanoparticles for Cell Entry

Abstract

Small interfering RNA (siRNA) holds great promise as a simple, yet powerful therapeutic strategy to knockdown the function of a particular gene. However, the major obstacle to the use of siRNA in clinical applications is the lack of an effective delivery system. Much effort has concentrated on developing methods to package or encapsulate siRNA with polymers or lipids. In a recent issue of Nature Materials, Paula Hammond and coworkers present an innovative approach to siRNA delivery based on the production of dense RNA “microsponges” that contain more than a half million copies of an siRNA precursor.1 The morphology of these microsponges resembles that of spherulites: assemblies of linear polymers in which highly ordered pleated lamellar sheets, interspersed with amorphous regions, radiate outward from a nucleating core to form a roughly spherical aggregate. The innovative strategy demonstrates improvements in RNA production, payload encapsulation, and transport and cell entry.