PHILADELPHIA- A $14M grant will fund research on gene-editing therapies for rare metabolic diseases at the Perelman School of Medicine at the University of Pennsylvania (Penn) and Children's Hospital of Philadelphia (CHOP). The research will focus specifically on developing therapies for urea cycle disorders, which impact roughly 1 in every 35,000 children. Using a form of CRISPR technology, the ultimate vision of the four-year grant is to create a platform for rapid development of personalized gene-editing therapies for a wide range of rare genetic disorders.
The grant, funded by the National Institutes of Health through its Somatic Cell Genome Editing Program (SCGE), will support research to further advance prime editing, a new and more versatile form of CRISPR technology. Unlike previous gene-editing methods, prime editing allows precise changes to the genome, correcting any genetic mutation rather than just swapping out individual chemical bases of DNA. This technology holds the promise of personalized treatments for patients with rare metabolic diseases such as type I citrullinemia, ASA lyase deficiency, and CPS1 deficiency. These life-threatening conditions, characterized by the body's inability to fully break down proteins, often lead to toxic ammonia buildup, causing brain damage, coma, or even death if untreated.
Despite previous attempts to treat these diseases through gene therapy, success has been limited due to immune responses to current therapies. Prime editing could change this by enabling permanent genetic corrections. "With this technology, we hope to not just manage symptoms, but offer a durable, potentially lifelong cure for these children," said Kiran Musunuru, MD, PhD, a professor of Cardiovascular Medicine and Director of Penn Cardiovascular Institute's Genetic and Epigenetic Origins of Disease Program.
"We're not just focusing on one specific disease," said Rebecca Ahrens-Nicklas, MD, PhD, an attending physician with the Metabolic Disease Program and the Division of Human Genetics at CHOP. "We're focusing on the patient in front of us, whatever variant they have. This approach enables us to treat a wider array of patients who've previously had no options."
The SCGE program is designed to address diseases caused by genetic changes. During its first phase (2018-2023), the program developed tools to perform genome editing in somatic cells which are non-reproductive cells in the body. Now in its second phase, SCGE seeks to bring genome-editing therapies from the lab to the clinic.
The team, which has previously received funding from the SCGE, aims to begin clinical trials within the next four years, marking an exciting new chapter in the field of precision medicine.
