The W.M. Keck Foundation has awarded a $1.2 million grant to medicinal chemistry and computational biology researchers at the University of Kansas and the University of Chicago focused on addressing a long-unresolved problem in biomedical research—finding molecules able to target the “undruggable proteome.”
KU School of Pharmacy Assistant Professor of Medicinal Chemistry Jingxin Wang applied for and received the Keck funding jointly with University of Chicago Assistant Professor of Medicine and Human Genetics, Yang Li. Using a type of molecule called RNA splicing modulators coupled with deep learning models, their research holds promise to be a game-changer in drug development and disease research. The pair of researchers and their lab colleagues are working to identify human genes, and particularly, sequences among those genes, that will respond to drug therapies that target an essential biological process in humans called RNA splicing. It could open the door to successful new disease therapies and cures.
“Approximately 70 percent of the proteome (the entire set of proteins in certain human tissues) cannot be targeted by a drug,” explained Wang. “This is alarming because we sometimes know how disease happens, but we don't have any method to treat the disease. This is basically the undruggable proteome problem in medicinal chemistry.”
Wang’s and Li’s research seeks to address the undruggable problem. Recently, several RNA splicing modulators have been approved by the Food and Drug Administration (FDA) for the life-saving treatment of previously untreatable spinal muscular atrophy and Duchenne muscular dystrophy.
“If we can precisely map where we can target RNA splicing, then researchers can focus on those genes and RNA sequences for drug development,” said Wang. “After systematic investigation, we will have a comprehensive map of splicing regulatory sequences for the whole human genome, and this will be a very valuable resource, not only for us but for the entire research community.”
The biochemical process in human cell development and replication is a complex system at the molecular level. Genes are encoded in DNA (deoxyribonucleic acid), which is almost identical in all human cells. DNA passes on the genetic information to RNA (ribonucleic acid) in a process called transcription. Then, RNA translates the encoded genetic information to protein in our cells. The proteins usually act as final “executors” that perform or regulate most cell functions.
