A $14 million grant from the National Institutes of Health (NIH) will fund research at the Perelman School of Medicine at the University of Pennsylvania (Penn) and Children's Hospital of Philadelphia (CHOP) to develop gene-editing therapies for rare metabolic diseases. The four-year project will focus on urea cycle disorders, which affect approximately 1 in 35,000 children, with the goal of creating a platform for rapid development of personalized gene-editing therapies using CRISPR technology.
Advancing Prime Editing Technology
The grant, awarded through the NIH's Somatic Cell Genome Editing Program (SCGE), will support the advancement of prime editing, a more versatile form of CRISPR technology. Unlike previous methods that swap individual DNA bases, prime editing allows for precise genomic alterations, correcting any genetic mutation. This is particularly relevant for rare metabolic diseases such as type I citrullinemia, ASA lyase deficiency, and CPS1 deficiency, where the body cannot fully break down proteins, leading to toxic ammonia buildup and potentially fatal consequences.
Potential for Lifelong Cures
Previous attempts to treat these diseases with gene therapy have been hampered by immune responses. Prime editing offers the potential for permanent genetic corrections, potentially providing lifelong cures. According to Kiran Musunuru, MD, PhD, a professor at Penn, the aim is to "not just manage symptoms, but offer a durable, potentially lifelong cure for these children."
Personalized Approach to Treatment
The research emphasizes a personalized approach, focusing on individual patient variants rather than specific diseases. Rebecca Ahrens-Nicklas, MD, PhD, an attending physician at CHOP, stated, "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."
From Lab to Clinic
The SCGE program aims to translate genome-editing therapies from the laboratory to clinical application. The research team, having previously received funding from the SCGE, plans to initiate clinical trials within the next four years, representing a significant advancement in precision medicine.
