A scientist from the Florida campus of The Scripps Research Institute has been awarded $1.5 million from the National Institutes of Health to develop new computer-driven design methods to find new therapeutics targeting RNA. Matthew Disney, Ph.D., an associate professor at Scripps Research, is the principal investigator for the four-year study. RNA was once considered a passive messenger, used only to carry copies of the DNA needed to produce or translate proteins. All that changed when it was found that RNA could produce chemical reactions that, for example, cause proteins to fold into various forms. RNA is an increasingly important potential target for the design of small molecule therapeutics, although methods to design small molecule drugs that bind to RNA and affect its function are still in their infancy. "The rational design of small molecules that exploit therapeutic targets from genomic sequence was one of the promises of the human genome project, but people had no idea of how to do it," Dr. Disney said. "As a result, most targets—especially RNA targets—represent untapped potential." A computer program created by Dr. Disney merges information on the interaction between small molecules (potential drugs) and RNA folds that contribute to specific diseases. Disney said his approach differs from conventional "top-down" methods that normally screen an RNA target against a broad chemical library. "Our bottom-up approach uses information about the small RNA motifs such as internal loops or hairpins that a small molecule ligand prefers to bind," he said. Using this method, Dr. Disney recently successfully designed several small molecules that are strongly active against myotonic dystrophy type 1, the most common form of muscular dystrophy.
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