Dr. Graham Erwin, an assistant professor in the department of molecular and human genetics at Baylor College of Medicine, has been named a recipient of the National Institutes of Health (NIH) Director’s New Innovator Award. The award, which is part of the NIH Common Fund’s High-Risk, High-Reward Research program, provides $2.4 million in funding to support innovative projects by early career scientists.
Erwin's research centers on developing small molecules capable of editing the human genome to correct pathogenic mutations. His earlier work led to the creation of synthetic transcription elongation factors (Syn-TEFs), which target DNA repeats that silence gene expression in Friedreich ataxia—a neurodegenerative disease currently lacking effective treatments. In cell and animal models, these molecules were shown to restore normal gene function by binding to the problematic DNA sequence and recruiting proteins needed for proper gene expression. A derivative of this molecule is now being tested in Phase 1 clinical trials for Friedreich ataxia patients.
Building on his previous findings, Erwin's new project aims to synthesize and evaluate a molecule that can bind directly to DNA and contract repetitive sequences back to their normal length. He described this approach as similar to using "molecular scissors." According to Erwin: “In our previous work, if the molecule is successful, patients would have to take the drug for life to maintain protein expression and halt progression of disease. Our goal with this work is to permanently correct the mutation and restore protein expression forever.”
Unlike established gene-editing techniques such as CRISPR-Cas9—which require large viral vectors for delivery into cells and can sometimes trigger immune reactions—Erwin’s small-molecule method does not need such vehicles. He explained: “Our small, organic molecules don’t require a delivery vehicle. These molecules can transiently get into the cell. Small molecules have been well-studied and are significantly less likely to trigger serious immune responses. They also often penetrate tissue more easily than larger vectors.”
The initial focus remains on cell models of Friedreich ataxia, but Erwin noted that if successful, this technique could be adapted for other conditions involving abnormal repetitive DNA sequences. “These small molecules are rationally designed, so they can be programmed to target another repetitive DNA sequence in a different disease,” he said.
More information about the NIH High-Risk, High-Reward Research program is available on their official website: https://commonfund.nih.gov/highrisk.
