During the first year Daniel Gao, PhD, was at Pitt, he was fortunate to build a team of researchers with diverse backgrounds who share a passion for understanding fundamental biological questions, developing molecular medicines, and ultimately benefiting patients.
“It’s been a genuine joy working and discussing science with them,” Dr. Gao said. “We’ve also been able to launch several exciting projects.”
Dr. Gao’s lab focuses on scalable genome engineering to address pathogenic genes with a large number of disease-causing variants in inherited retinal disease (IRD). “Take retinitis pigmentosa (RP), for example – a major form of IRD involving mutations in more than 80 genes,” he explained. “Despite promising pre-clinical progress correcting individual mutations one at a time, current gene editing therapies remain largely mutation or gene-specific, meaning a treatment developed for one variant often doesn’t help the next patient.”
To address this, the lab is building prime editing and integrase-based tools that enable precise, programmable insertion of therapeutic genes at safe-harbor or endogenous genomic loci in humans, independent of which mutation a patient carries. As Dr. Gao described, the hope for patients is that a single therapeutic strategy would benefit many genetically distinct forms of RP rather than requiring a bespoke therapy for each mutation. This has important implications for the cost and scalability of genomic medicine.
To sum up, “our work spans understanding genetic variants, engineering therapeutic cargo (editors), and developing delivery vehicles to translate these approaches from in-vitro studies into pre-clinical models,” Dr. Gao said.
Dr. Gao’s group is fortunate to collaborate with Drs. Byrne, Ait-Ali, and Sahel within the Department of Ophthalmology, as well as other scientists at Pitt, Boston University, and the University of Southern California.