Improved airway-targeted gene delivery in a pig model of cystic fibrosis
Cystic fibrosis (CF) is characterized by accumulation of thick mucus in the lungs and is associated with a high incidence of bacterial infection. Mutations in the gene encoding CF transmembrane conductance regulator (CFTR) underlie the disease. Gene therapy to deliver a normal copy of the CFTR gene has shown promise in both pre-clinical models and clinical trials; however, current gene delivery methods are inefficient and do not result in sustained expression of functional CFTR in the airways. Two studies in this issue of JCI Insight report the development and use of viral vector-based delivery of CFTR in pig models of CF. A team led by Patrick Sinn and Paul McCray Jr. of the University of Iowa developed a lentiviral-based vector that was delivered through the nose to newborn CF pigs. Analysis of these animals revealed evidence of functional CFTR expression in the airways. A second team led by Joseph Zabner of the University of Iowa and David Schaffer of the University of California, Berkeley, generated an adeno-associated virus (AAV) that homes to the pig airway to mediate expression of functional CFTR in the airways of 1 week-old CF pigs. Together, these reports indicate that viral vector-based approaches could potentially improve the effectiveness of CFTR gene therapy.
Lentiviral-mediated phenotypic correction of cystic fibrosis pigs
Paul B. McCray, Jr.
The University of Iowa
Patrick L. Sinn
The University of Iowa
View this article at: http://insight.jci.org/articles/view/88730?key=b4689e6b7aedc95452bc
CFTR gene transfer with AAV improves early cystic fibrosis pig phenotypes
University of Iowa Carver College of Medicine
University of California, Berkeley
View this article at: http://insight.jci.org/articles/view/88728?key=7e8c808d25cd5e3b5597
JCI Insight is the newest publication from the American Society of Clinical Investigation, a nonprofit honor organization of physician-scientists. JCI Insight is dedicated to publishing a range of translational biomedical research with an emphasis on rigorous experimental methods and data reporting. All articles published in JCI Insight are freely available at the time of publication. For more information about JCI Insight and all of the latest articles go to http://www.insight.jci.org.