4.5 Article

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

Journal

JOURNAL OF GENE MEDICINE
Volume 18, Issue 1-3, Pages 38-44

Publisher

WILEY
DOI: 10.1002/jgm.2874

Keywords

adenovirus; alpha-1 antitrypsin; gene therapy

Funding

  1. NIH Grant [5 T32 HL007873]

Ask authors/readers for more resources

Background 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. Methods In the present study, we use a modified pulmonary targeted adenovirus to express human alpha-1 antitrypsin (A1AT) in C57BL/6 J mice. Results 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 vectortargeted end organ. Conclusions 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 hepatic viral transduction and associated toxicities. Copyright (C) 2016 John Wiley & Sons, Ltd.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available