Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded a $2.5 million grant from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) to design precision drug candidates that target disease-associated RNAs.

TSRI is one of the world's largest independent, not-for-profit organisations focusing on research in the biomedical sciences. Matthew Disney, a TSRI professor, will be the principal investigator for the new four-year study.

“A major goal of genome sequencing efforts is to develop drug targets that could enable the development of patient-specific therapies,” Disney said. “In this project, we are developing quick ways to convert this information into lead drugs by using several novel and transformative technologies we developed. The new grant will keep us moving forward and allow us to tackle many new challenges in the area of precision medicine.”

While to date large macromolecules have generally been used to target RNA, small molecules can pass through the blood-brain barrier, a critical factor in the treatment of neurological diseases and cancer that affects the brain.

The Disney lab’s untraditional approach has been broadly applicable in developing precision probes to target disease-causing RNA repeat expansions, which cause more than 30 diseases—including Huntington’s, which has no cure—affecting millions worldwide.

Disney’s successful efforts in identifying various drug-like small molecules that bind to RNA is the result of his lab’s broad, bottom-up, computational approach known as Inforna, which can deep mine information against such genome sequences and cellular RNAs.

The new grant will enable Disney and his team to further investigate the manipulation of microRNAs. Discovered only in the 1990s, microRNAs are short molecules that work within virtually all animal and plant cells. Typically, each one functions as a “dimmer switch” for one or more genes, binding to the transcripts of those genes and effectively keeping them from being translated into proteins.

The new grant will also allow Disney to expand development of small molecules that target two miRNAs with a single small molecule and to study the cellular consequences targeting multiple disease pathways using what he calls a “designer poly-pharmacy approach.”