The Nobel Prize-winning discovery of RNA interference's ability to shut down genes and treat diseases was very promising almost a decade ago. But the complications that arose in the years after showcased the importance of delivery mechanisms because getting the genetic material inside the nucleus proved more difficult than it seemed.
While others have used means such as nanotechnology and conjugates to bring RNAi drugs into the cells, researchers at the University of California in San Diego have developed a way to disguise the genetic material itself so that it can enter cells and shut down genetic diseases at the core.
Because they hold a negative charge due to phosphate groups on their surfaces, RNAi drugs are repelled by the cell membrane, according to the university. So by masking that charge the scientists were able to get them past that checkpoint. By adding a phosphotriester group to the RNA, they neutralized the charge, making them more efficient at bypassing the membrane. This they called a small interfering ribonucleic neutral, or siRNN.
"Many current approaches use nanoparticles to deliver RNAi drugs into cells," lead researcher Stephen Dowdy said in a statement. "While nanotechnology protects the RNAi drug, from a molecular perspective nanoparticles are huge, some 5,000 times larger than the RNAi drug itself. Think of delivering a package into your house by having an 18-wheeler truck drive it through your living room wall--that's nanoparticles carrying standard RNAi drugs. Now think of a package being slipped through the mail slot--that's siRNNs."
In mice, the siRNNs were significantly more effective at blocking a target protein than other RNAi drugs, according to the university. Solstice Biologics, based in La Jolla, CA, has spun off with this technology, and is working to tailor it for cancer, viral infections and genetic diseases.
- here's the UCSD report