Dr. Graham Erwin, an assistant professor of molecular and human genetics at Baylor College of Medicine, has received the prestigious National Institutes of Health (NIH) Director’s New Innovator Award. This award, which grants $2.4 million to select early career scientists, supports innovative research approaches often overlooked by traditional funding sources. The funding will enable Erwin to expand his groundbreaking work on editing the human genome and correcting pathogenic mutations.
Erwin’s current research focuses on the potential of small molecules to address genetic issues at their source. His approach builds on previous successes, including a notable study published in Science in 2017. In that work, Erwin and his team developed synthetic transcription elongation factors, known as Syn-TEFs, which target a specific DNA repeat responsible for silencing frataxin expression in patients suffering from Friedreich ataxia, a severe neurodegenerative disorder without an effective treatment.
In their experiments using cell and animal models, the researchers demonstrated that Syn-TEFs could effectively bind to the problematic DNA repeat and recruit other proteins necessary for restoring normal frataxin production. This innovative work has led to the development of an analog of the molecule currently undergoing Phase 1 clinical trials for Friedreich ataxia patients.
Advancing Gene Editing Techniques
The latest phase of Erwin’s research aims to create a new molecule capable of binding to DNA and reducing the length of harmful repeated sequences back to normal. He likens this technique to “molecular scissors,” emphasizing its potential to provide a permanent solution for genetic mutations.
“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,” Erwin explained. “Our goal with this work is to permanently correct the mutation and restore protein expression forever.”
While other gene-editing technologies, such as CRISPR-Cas9, also aim to permanently alter DNA mutations, Erwin’s small-molecule method offers distinct advantages. Given the large size of CRISPR-Cas9, it requires a substantial delivery system, typically a viral vector, to enter cells. However, these vectors can sometimes induce severe immune responses in patients.
“Our small, organic molecules don’t require a delivery vehicle. These molecules can transiently get into the cell,” Erwin noted. “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.”
Erwin will primarily focus his investigations on cell models of Friedreich ataxia. Yet, if successful, the technique could extend to treat numerous other diseases. Currently, sixty known human diseases are linked to abnormalities in 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 added.
Through the NIH New Innovator Award, Dr. Graham Erwin is poised to make significant advancements in gene editing, potentially transforming therapies for various genetic disorders.
