A Wayne State University School of Medicine researcher in the Department of Physiology was awarded a new four-year, $2.69 million grant from the National Heart, Lung and Blood Institute to generate an animal model carrying the most common mutation in patients with cystic fibrosis.
Fei Sun, M.D., Ph.D., the research project's principal investigator and an assistant professor, also will test the efficacy of therapeutic reagents for cystic fibrosis drug discovery.
The Cystic Fibrosis Foundation approved additional funding to Dr. Sun's lab, to generate rabbits carrying the second most common mutation in cystic fibrosis patients, and to test potential therapeutic drugs in the animal model, awarding $413,068 to be used through Oct. 31, 2017.
Cystic fibrosis is a progressive genetic disease that causes persistent lung infections and, over time, limits the ability to breath. It is caused by mutations of gene encoding cystic fibrosis transmembrane conductance regulator, or CFTR, Dr. Sun said. According to the Cystic Fibrosis Foundation Patient Registry, more than 70,000 people worldwide are living with the disease, and approximately 1,000 new cases are diagnosed each year, often by age 2. The first drug targeting the basic genetic defect in CF, a CFTR modulator, was approved in 2012.
"Research on cystic fibrosis animal models has contributed significantly to understanding the mechanism of underlying disease," Dr. Sun said. "However, existing CF animal models have their limitations, either because the animal models fail to reproduce human phenotypes or because the animal models have very high maintenance costs and need specialized care."
The goal for the first year of the project funded by the NHLBI (R01HL133162) is to generate CF rabbits carrying the CF mutation called knockin, using CRISPR/Cas9 gene editing technology.
"Using CRISPR/Cas9 gene editing technology, we have developed the first CF rabbits carrying no CFTR gene (CFTR gene knockout) in the world. Initial work on the rabbits revealed a spectrum of clinical presentations that is similar to that in human CF patients," Dr. Sun said. "The goals of this grant are to generate rabbits carrying the most common mutation in CF patients, F508del CFTR (CF mutation knockin), to characterize the CF rabbits and to test the efficacy of therapeutic reagents for CF drug discovery."