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Eur J Cardiothorac Surg 2001;20:159-163
© 2001 Elsevier Science NL

Efficiency of non-viral gene delivery systems to rat lungs

A.N. Uduehi, U. Stammberger, S. Frese, R.A. Schmid

Division of General Thoracic Surgery, University Hospital, Bern, Switzerland

Received 22 September 2000; received in revised form 16 March 2001; accepted 23 March 2001.

Corresponding author. Tel.: +41-31-632-2330; fax: +41-31-632-2327
e-mail: ralph.schmid{at}insel.ch

Objective: Transient expression of therapeutic genes within lung allografts may modulate the pathological processes following allotransplantation. Whilst efficient gene transfer to lungs has been reported with viral vectors, their usefulness is limited on the grounds of safety. Since non-viral systems overcome many of these safety issues, our studies were designed to evaluate the efficiency of several non-viral gene delivery vectors for in vivo transfer of plasmid DNA to rat lungs via the airways. Methods: Fischer rats (230–260 g) underwent a thoracotomy, right main bronchus occlusion and instillation of 300 µg naked or complexed DNA (pCIluci, luciferase gene/CMV promoter) to the left lung followed by ventilation for 10 min. Rats were divided into five treatment groups (n=5): (1) Glucose, (2) Naked DNA, (3) Linear polyethylenimine (PEI), (4) Branched PEI, (5) Lipid GL-67/DOPE and (6) DOTAP/cholesterol. Animals were sacrificed 24 h after gene delivery for measurement of reporter gene activity and gas exchange of the left lung. Results: Linear PEI was the most efficient gene delivery vector and was significantly better than DOTAP/cholesterol (P=0.00002) and naked DNA (P=0.004). All gene delivery vectors impaired function of the transfected left lung compared with DNA alone. Of all the gene delivery vectors tested, lipid GL-67/DOPE exerted the least effect on lung function whilst DOTAP/cholesterol mediated the most adverse effect. Conclusion: Linear PEI was the most efficient vector for gene delivery to rat lungs in our experimental setting although it mediated a moderate impairment in lung function. Further studies are needed to evaluate whether this effect is transient.

Key Words: Cationic liposomes • Cationic polymers • Plasmid DNA • Non-viral gene delivery






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Copyright © 2001 European Association for Cardio-Thoracic Surgery. Published by Elsevier. All rights reserved.