Pulmonary vasculature directed adenovirus increases epithelial lining fluid alpha-1 antitrypsin levels

The Journal of Gene Medicine
Maurizio BuggioDavid T Curiel

Abstract

Gene therapy for inherited serum deficiency disorders has previously been limited by the balance between obtaining adequate expression and causing hepatic toxicity. Our group has previously described modifications of a replication deficient human adenovirus serotype 5 that increase pulmonary vasculature transgene expression. In the present study, we use a modified pulmonary targeted adenovirus to express human alpha-1 antitrypsin (A1AT) in C57BL/6 J mice. Using the targeted adenovirus, we were able to achieve similar increases in serum A1AT levels with less liver viral uptake. We also increased pulmonary epithelial lining fluid A1AT levels by more than an order of magnitude compared to that of untargeted adenovirus expressing A1AT in a mouse model. These gains are achieved along with evidence of decreased systemic inflammation and no evidence for increased inflammation within the vector-targeted end organ. In addition to comprising a step towards clinically viable gene therapy for A1AT, maximization of protein production at the site of action represents a significant technical advancement in the field of systemically delivered pulmonary targeted gene therapy. It also provides an alternative to the previous limitations of hepati...Continue Reading

References

Apr 23, 1987·The New England Journal of Medicine·M D WewersR G Crystal
Jun 1, 1994·Japanese Journal of Medical Science & Biology·Y KanegaeI Saito
Nov 13, 1998·Journal of Virology·W XiaoJ M Wilson
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·S SongT R Flotte
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·N MorralA L Beaudet
Aug 3, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·S M StollM P Calos
Oct 15, 2003·Journal of Virology·Natalya BelousovaVictor Krasnykh
Jun 17, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Simon F De MeyerKaren Vanhoorelbeke
Jun 21, 2008·Orphanet Journal of Rare Diseases·Laura Fregonese, Jan Stolk
Aug 9, 2008·The Journal of Clinical Investigation·Salima Hacein-Bey-AbinaMarina Cavazzana-Calvo
Mar 25, 2009·Human Gene Therapy·Mario CooperRoland W Herzog
Apr 29, 2011·Gene Therapy·M Gonzalez-AparicioR Hernandez-Alcoceba
Jul 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sunday OladipupoJeffrey M Arbeit
Jan 26, 2012·The Journal of Infectious Diseases·Geraldine A O'HaraAdrian V S Hill
Apr 25, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ian MorecroftMargaret R Maclean
Jan 29, 2013·Journal of Experimental & Clinical Cancer Research : CR·Fang WeiQian Huang
Aug 15, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Thipparat SuwanmaneeTal Kafri
Jun 24, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Zhi Hong LuJeffrey M Arbeit

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Citations

Jul 16, 2020·American Journal of Respiratory Cell and Molecular Biology·Reka Lorincz, David T Curiel

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