|Title||High-Efficiency, Selection-free Gene Repair in Airway Stem Cells from Cystic Fibrosis Patients Rescues CFTR Function in Differentiated Epithelia.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Vaidyanathan S, Salahudeen AA, Sellers ZM, Bravo DT, Choi SS, Batish A, Le W, Baik R, de la O S, Kaushik MP, Galper N, Lee CM, Teran CA, Yoo JH, Bao G, Chang EH, Patel ZM, Hwang PH, Wine JJ, Milla CE, Desai TJ, Nayak JV, Kuo CJ, Porteus MH|
|Journal||Cell Stem Cell|
|Date Published||2020 02 06|
|Keywords||Animals, Cell Differentiation, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Epithelial Cells, Epithelium, Humans, Stem Cells, Swine|
Cystic fibrosis (CF) is a monogenic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Mortality in CF patients is mostly due to respiratory sequelae. Challenges with gene delivery have limited attempts to treat CF using in vivo gene therapy, and low correction levels have hindered ex vivo gene therapy efforts. We have used Cas9 and adeno-associated virus 6 to correct the ΔF508 mutation in readily accessible upper-airway basal stem cells (UABCs) obtained from CF patients. On average, we achieved 30%-50% allelic correction in UABCs and bronchial epithelial cells (HBECs) from 10 CF patients and observed 20%-50% CFTR function relative to non-CF controls in differentiated epithelia. Furthermore, we successfully embedded the corrected UABCs on an FDA-approved porcine small intestinal submucosal membrane (pSIS), and they retained differentiation capacity. This study supports further development of genetically corrected autologous airway stem cell transplant as a treatment for CF.
|Alternate Journal||Cell Stem Cell|
High-Efficiency, Selection-free Gene Repair in Airway Stem Cells from Cystic Fibrosis Patients Rescues CFTR Function in Differentiated Epithelia.
Eugene H. Chang, MD