Seventh Framework Programme - European Union
An EU consortium to identify novel targets and drugs for cancer treatment

Tools and technology:
New tools: RNAi

By Brona McVittie

Within the past decade scientists have been uncovering the natural ways and means that cells regulate gene expression. RNA interference (RNAi) was discovered because of the responses a cell has to viral infection. Viruses often possess a double-stranded RNA genome. “This is different from the single-stranded RNA normally present in our cells,” explains Barry. “Luckily our cells recognise the double-stranded viral RNA and initiate a program of RNAi to destroy it.”

In 2006 Fire and Mello were awarded a Nobel prize for describing how RNAi works in worms (link). “Researchers now employ the technique to silence genes by making double-stranded RNA versions of them and expressing these in cells. Although it’s still not fully understood,” says Barry, “it clearly involves destruction of the normal messenger RNA, thereby blocking the conversion of DNA to protein.”

Double-stranded RNA only triggers the disintegration of mRNA with the same sequence. "The double-stranded RNA gets chopped up into small pieces, called small interfering RNAs (siRNAs)." These coding fragments become embedded in a protein complex called RISC, helping it to target the right mRNA, which RISC then degrades.

siRNAs were first discovered in plants by David Baulcombe’s group at the John Innes Centre in Norwich. Later Thomas Tuschl (Max Planck Institute, Göttingen) showed that custom-made synthetic siRNAs could induce RNAi in mammalian cells. Now, the technology is being widely used in basic science as a method to study the function of genes with the possibility of novel therapies in the future

“Now we can silence any gene in the genome with reagents that we design from scratch,” affirms Michael Boutros. The way this affects a cell will reveal something about the gene function. “RNAi screening will help us to uncover components of signaling networks that are important in cancer so we can find potential drug targets.”