SNIPPETS of RNA that switch off disease-causing genes can now slip into cells unaided. This could help efforts to use RNA interference (RNAi) to treat diseases such as cancer and diabetes.
For a gene to be expressed as a protein, it must first be copied into messenger RNA (mRNA). RNAi blocks this process by sending in RNA snippets that bind to specific mRNAs.
To do this, the gene-blocking RNA must first get into the cell. A variety of elaborate strategies have been suggested as ways to get it there, such as attaching the blocking RNA to fragments of bacteria or carbon nanotubes. Now Anastasia Khvorova and colleagues at in Worcester, Massachusetts, have come up with a simpler approach.
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RNA molecules cannot easily pass unaided into cells because they are charged or 鈥減olar鈥�; this means they dissolve easily in water but not fats. To cross the cell membrane, molecules need to be soluble in both.
So Khvorova鈥檚 team chemically modified RNA molecules to reduce their negative charge, and make them smaller (see diagram). This seemed to do the trick. 鈥淭hese compounds get inside the cell within seconds,鈥� says Khvorova, who presented her work at an in Keystone, Colorado, last month.
RXi says that in studies of human and animal cells its molecules have been shown to block at least 17 genes, some of which are implicated in disease. It hopes to find many more, but the unusually short strands of RNA it uses may not be able to block the RNA of all genes.
Studies in mice show that the molecules can enter many different cell types, including immune, eye and liver cells, and switch off genes there, RXi says. However, to tackle cancer or inflammatory disease, RXi鈥檚 RNA would have to be injected into the bloodstream. From there it might find its way not just into cancer cells, for example, but also into healthy cells, and block genes there, warns at the City of Hope cancer centre in Duarte, California, who researches an alternative approach to RNAi. Even for diseases where the RNA could be injected directly into target tissue, it might still reach cells other than the intended ones.
Rossi adds, however, that RXi鈥檚 self-delivering RNA might be useful in cell-culture or animal experiments as a means of rapidly screening RNA sequences to find candidates that could be delivered by other means.
