Inefficient gene transfer by adenovirus vector to cystic fibrosis airway epithelia of mice and humans
- 1 October 1994
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 371 (6500) , 802-806
- https://doi.org/10.1038/371802a0
Abstract
THE success of adenoviral vectors for gene therapy of lung disease in cystic fibrosis (CF) depends on efficient transfer of the complementary DNA encoding the correct version of the cystic fibrosis transmembrane regulator (CFTR) to the affected columnar epithelial cells lining the airways of the lung. Pre-clinical studies in vitro suggest that low doses of adenovirus vectors carrying this CFTR cDNA can correct defective Cl− transport in cultured human CF airway epithelia1. Here we use mice carrying the disrupted CF gene2 to test the efficacy of this transfer system in vivo. We find that even repeated high doses can only partially (50%) correct the CF defect in Cl− transport in vivo and do not correct the Na+ transport defect at all. We investigated this discrepancy between the in vivo and in vitro transfer efficiency using CF mouse and human samples, and found that it reflects a difference in the susceptibility to adenovirus-5 transduction of the epithelial cell types dosed in vivo (columnar) and in vitro (basal-cell-like). These studies indicate that more efficient adenoviral gene-transfer vectors and/or refinement of dosing strategies are needed for therapy of CF lung disease.Keywords
This publication has 21 references indexed in Scilit:
- Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosisNature Genetics, 1994
- Gene Therapy for Cystic Fibrosis Using E1-Deleted Adenovirus: A Phase I Trial in the Nasal Cavity. University of North Carolina at Chapel Hill, Chapel Hill, North CarolinaHuman Gene Therapy, 1994
- Correction of cAMP-Stimulated Fluid Secretion in Cystic Fibrosis Airway Epithelia: Efficiency of Adenovirus-Mediated Gene Transfer In VitroHuman Gene Therapy, 1994
- Gene Therapy of Cystic Fibrosis Lung Disease Using E1 Deleted Adenoviruses: A Phase I Trial. University of Michigan, Ann Arbor, Michigan and University of Pennsylvania, Philadelphia, PennsylvaniaHuman Gene Therapy, 1994
- Safety and efficacy of repetitive adenovirus–mediated transfer of CFTR cDNA to airway epithelia of primates and cotton ratsNature Genetics, 1994
- Lung Gene Therapy: In Vivo Adenovirus-Mediated Gene Transfer to Rhesus Monkey Airway EpitheliumHuman Gene Therapy, 1994
- Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosisPublished by Elsevier ,1993
- Direct gene transfer of human CFTR into human bronchial epithelia of xenografts with E1–deleted adenovirusesNature Genetics, 1993
- Two steps closer to gene therapy for cystic fibrosisNature Genetics, 1992
- Increased Bioelectric Potential Difference across Respiratory Epithelia in Cystic FibrosisNew England Journal of Medicine, 1981