Over a decade, researchers have been working on RNA interference to treat cancer. However, short interfering (siRNA), which defends RNA viruses, gets degraded by enzymes in the body.
"A cluster of microsponges made of long strands of folded RNA, as seen by scanning electron microscopy. Image: Hammond laboratory "
Paula Hammond of MIT and her team have discovered a new system to deliver RNA, which has been densely packed within microspheres to reach the target site without degradation. With low particle doses, the specific gene expression gets knocked down by the system.
A number of researches have been done to target specific site using siRNA. Usually, siRNA is packed into nanoparticles like gold. However, it was difficult to intensely pack the short strands of siRNA.
The team used rolling circle transcription process to overcome this problem and a long strand of RNA, which can be folded into a small, dense sphere, was synthesized. The strand consists of repeated sequences of 21 nucleotides.
These long strands have a capability to fold into sheets and subsequently, to self assemble as a sponge- like, compact sphere. Within a diameter of 2 µm, around 500000 of the repeated sequence can be packed. A positively charged polymer has been layered over the spheres to promote dense packaging and to minimize the size to 200 nm. This supports the entry of spheres into cells.
As the sphere enters the cells, an enzyme Dicer, recognizes and cleaves the repeated sequence at specific areas.
The research team used mice to examine their RNA sphere. The sphere was programmed to release RNA sequences that knocked down a gene that makes cancer cells to glow in mice. This mechanism used a thousand times lesser nanoparticles when compared to traditional methods.
It has been found that the blood vessels around the tumor cells have small pores, through which the microspheres can enter, accumulate and deliver nanoparticles.
The paper has been published in Nature Materials journal this week.