Mini-Gene Therapy for Cystic Fibrosis

Shortened versions of the normal cystic fibrosis transmembrane regulator (CFTR) can function like normal, full-length protein in experimental models of cystic fibrosis (CF) disease, according to researchers at the University of Iowa (UI, Iowa City, USA; www.uiowa.edu). This finding may lead to strategies that could make gene therapy for CF a reality.

Despite the advantages of an adeno-associated virus (AAV) as a vector for gene therapy for CF, AAV is too small to accommodate the normal CFTR gene. The researchers made a series of mini-CFTR genes that produce shortened protein in airway cells by deleting parts of the CFTR protein from a region called the R domain. Two model CF cell systems were used to test the ability of the shortened proteins to act like normal, full-length CFTR in airway cells. The experimental models are designed to mimic airway cells in humans with CF. In both models, each mini-gene made protein with all the properties and function of the normal full-length protein. Additional studies are needed to generate an AAV vector that could prove useful in CF gene therapy.

"We proved that we could actually take out a fairly significant part of the domain without affecting the protein's ability to transport chloride ions and without affecting its ability to get to the right place in the cell to start working,” said Lynda S. Ostedgaard, Ph.D., UI associate research scientist in internal medicine and lead author of the study.