Breakthrough approach can quickly identify new drug candidates from genome sequence

Feb. 13, 2014

In research that could ultimately lead to new drug therapies, scientists from The Scripps Research Institute (TSRI) have developed an approach that could potentially be used to design drugs from genome sequence. The technique, described online in Nature Chemical Biology, has been dubbed Inforna.

“This is the first time therapeutic small molecules have been rationally designed from only an RNA sequence,” says Matthew Disney, PhD, who led the study. “We have shown that that approach allows for specific and unprecedented targeting of an RNA that causes cancer.”

Disney’s team has been developing approaches to understand the binding of drugs to RNA folds. In particular, the researchers are interested in manipulating microRNAs, short molecules that work within virtually all animal and plant cells. Typically each one functions as a “dimmer switch” for one or more genes; it binds to the transcripts of those genes and effectively keeps them from being translated into proteins. In this way microRNAs can regulate a wide variety of cellular processes. Some microRNAs have been associated with diseases; MiR-96 microRNA, for example, is thought to promote cancer by discouraging apoptosis.

The researchers developed computational approaches that can mine information against such genome sequences and all cellular RNAs with the goal of identifying drugs that target such disease-associated RNAs while leaving others unaffected. The new study describes their computational technique, which identifies optimal drug targets by mining a database of drug-RNA sequence interactions against thousands of cellular RNA sequences. Using Inforna, the researchers identified compounds that can target microRNA-96, as well as additional compounds that target nearly two dozen other disease-associated microRNAs. They showed that the drug candidate that inhibited microRNA-96 inhibited cancer cell growth, and that cells without functioning microRNA-96 were unaffected by the drug. Read the study abstract.

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