RNA interference (RNAi) is a naturally occurring process in cells that suppresses gene expression. Short interfering RNA (siRNA) binds to messenger RNA, which carries genetic information, and destroys it before it can be translated into protein. RNAi thereby provides a powerful tool for shutting off malfunctioning genes, and recent research has been focused on delivering siRNAs designed to target specific genes to treat diseases such as cancer.

A major challenge of developing treatment approaches based on RNAi is finding an efficient delivery system for the RNA. A team of researchers led by Paula T. Hammond (Massachusetts Institute of Technology, Cambridge) has searched for a way to tightly pack the short strands of siRNAs into nanoparticles small enough to make their way into target cells. “It's been a real struggle to try to design a delivery system that allows us to administer siRNA, especially if you want to target it to a specific part of the body,” Hammond said in a press release.

Now, the team has found a way to take advantage of the DNA/RNA machinery provided by nature. Using a method called rolling circle transcription, they produced long, pure RNA strands that could assemble themselves into a delivery system by winding up into compact spheres. These small spheres, which they call RNAi-microsponges, are so dense that they withstand degradation until they reach their destination in the body, where the RNA structures are converted into siRNA that can actively silence genes (Nat. Mater. doi: 10.1038/nmat3253; published online 26 February 2012).

The researchers tested the efficiency of their delivery system by designing RNA sequences targeting a gene that causes tumor cells to glow in mice. They delivered the highest number of siRNA molecular copies ever encapsulated in a nanoparticle, and the RNAi-microsponges significantly reduced expression of the targeted gene. Even with a smaller dose of particles, the new system could be used to knock down expression of specific genes as effectively as existing delivery methods.

These microsponges offer a way to treat cancer and other chronic diseases that may be caused by a faulty gene, without the negative effects of existing delivery methods. “RNA interference holds a huge amount of promise for a number of disorders, one of which is cancer, but also neurological disorders and immune disorders,” Hammond said. Next, the researchers are working to develop DNA-carrying spheres, which may be used in gene therapy approaches.