Efficiency of non-viral gene delivery systems to rat lungs

Uduehi, A.N.; Stammberger, U.; Schmid, R.A. (2001). Efficiency of non-viral gene delivery systems to rat lungs. European journal of cardio-thoracic surgery, 20(1), pp. 159-163. Elsevier Science B.V. 10.1016/S1010-7940(01)00714-X

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery

UniBE Contributor:

Stammberger, Uz Martin and Schmid, Ralph

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1010-7940

Publisher:

Elsevier Science B.V.

Language:

English

Submitter:

Marceline Brodmann

Date Deposited:

05 Oct 2020 15:39

Last Modified:

05 Oct 2020 15:39

Publisher DOI:

10.1016/S1010-7940(01)00714-X

BORIS DOI:

10.7892/boris.114978

URI:

https://boris.unibe.ch/id/eprint/114978

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