Scripps study reveals new RNA-drug targeting potential

In another step toward realizing the elusive potential of RNA drugs, scientists at the Scripps Research Institute have nailed down one of the mechanisms by which the gene-silencers reach their targets in the cell's nucleus.

RNA drugs can be a powerful weapon against many diseases, including viral infections and cancers, by silencing portions of the genetic code at the root of the problem. But researchers have struggled to perfect a delivery method that gets the drug to the target and enables the drug to act unhindered once it's there.

To uncover the mechanics behind this form of drug targeting, the Scripps researchers used the protein Argonaute 2, which destroys RNA transcripts of specific genes. Argonaute naturally grabs onto "guide RNA," short sequences of microRNA that act as a template telling the protein where to go. But unless the Argonaute protein unloads the microRNA upon reaching its target, it won't silence the gene as intended, according to a Scripps release.

So they introduced decoy target RNA sequences to nullify the activity of the microRNA strands, thus destabilizing their connection with the Argonaute protein. The researchers found that the presence of the decoy strands greatly hastened the unloading of the Argonaute protein, allowing it to work upon the intended target alone. This could be used to deliver pharmaceutical agents as a more powerful class of RNA inhibitor.

The exact way in which this happens is still a mystery, though, the researchers admit. But they are working on a structural study of the Argonaute complex as it hooks onto the miRNA in the first place. This could lead to a greater understanding of how RNA inhibition takes place and how it may be improved as a drug-delivering method.

- here's the release