Abstract
Although gene delivery to the pulmonary circulation has both experimental and therapeutic potential, the delivery methods, distribution of transgene, and subsequent inflammatory response have been poorly characterized to date. To address these issues, we utilized a 0.76-mm OD (outside diameter) end hole catheter inserted into the internal jugular vein of adult Sprague-Dawley rats, directing the tip into a pulmonary capillary wedge position. We then compared infusion of polycationic lipid:DNA complexes to replication-defective adenovirus with respect to magnitude and distribution of transgene expression using either chloramphenicol acetyltransferase (CAT) or human placental alkaline phosphatase (hpAP) reporter genes. Both lipid:DNA and adenovirus resulted in detectable transgene expression, though maximum lung CAT activity using lipid (gamma AP-DLRIE/DOPE) was approximately 2% of maximum activity using adenovirus (Ad-CAT). Further characterization of expression after transfection with 10(8) pfu (plaque forming units) of Ad-CAT demonstrated persistence of transgene for at least 14 days (lung CAT activity 27% of maximum). Alkaline phosphatase staining demonstrated that both large and small pulmonary arteries as well as the alveola...Continue Reading
Citations
Jan 13, 2006·Pflügers Archiv : European journal of physiology·Leifu JiangMarion Delcroix
Dec 28, 1999·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·S D CassiviS Keshavjee
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·H C ChampionP J Kadowitz
Oct 28, 1999·American Journal of Respiratory Cell and Molecular Biology·A I CampbellD J Stewart
Oct 28, 1999·American Journal of Respiratory Cell and Molecular Biology·B Fouty, D M Rodman
Jan 12, 2011·Expert Opinion on Biological Therapy·Paul N Reynolds
Aug 17, 2002·Biochimica Et Biophysica Acta·Ingrid N MichonJohan Kuiper
Mar 27, 2012·Current Opinion in Pharmacology·Dominik WiedemannThomas Schachner
Apr 27, 2010·Biochemical and Biophysical Research Communications·Levent M AkyürekElizabeth G Nabel
Sep 5, 2001·Nature Biotechnology·P N ReynoldsD T Curiel
Jun 2, 2000·Human Gene Therapy·S BadranJ J Rome
Oct 31, 2001·Circulation·A I CampbellD J Stewart
Apr 11, 2000·Gene Therapy·D GoulaB A Demeneix
Apr 22, 2003·Gene Therapy·J ZhangS Li
Feb 28, 2002·The Journal of Pharmacology and Experimental Therapeutics·Arnaud ScherpereelVladimir R Muzykantov
Apr 15, 2000·Annals of Internal Medicine·S M AlbeldaJ B Zuckerman
Sep 20, 2000·American Journal of Physiology. Heart and Circulatory Physiology·S S BolzU Pohl
Jul 17, 1999·The American Journal of Physiology·K X LiD M Rodman
Jul 17, 1999·The American Journal of Physiology·J L AschnerD W Busija
Dec 9, 2010·Molecular Pharmaceutics·Paul N Reynolds