Side-effects of a systemic injection of linear polyethylenimine-DNA complexes

International audienceBackground: Systemic administration of linear polyethylenimine-DNA complexes (L-PEI/DNA) results in transient expression of the transgene in the lung. In this study we analyzed the side effects associated with L-PEI-mediated transfection. Methods: Mice of weight ranging from 16 to 25 g received increasing amounts of L-PEI/DNA intravenously. Gene expression was evaluated using luciferase as a reporter gene. Toxicity was evaluated by monitoringthe appearance of a shock after injection, the survival of the animals and the microscopic damages in the tissues. Adherence of blood cells on the endothelium was measured after immuno-staining of the CD11b positive cells. Anti-aggregant treatments were used in order to prevent the formation of thrombi.Results: Increasing the quantity of L-PEI/DNA resulted in an important augmentation of the luciferase activity in the lung, but was associated with liver necrosis and death. Lethality was reached at lower doses in old mice than in the younger, suggesting also an influence of age. Transfection was associated with an augmentation of adhesion of CD11b positive cells on the endothelium, without evidence of lung injury. Anti-aggregant treatments (aspirin, EDTA, heparin or clopidogrel) decreased the L-PEI-mediated transfection, supporting the hypothesis that formation of thrombi was necessary for the blockade of DNA-complexes in the lung capillaries and subsequent transfection of lung cells.Conclusion: This study demonstrates that L-PEI/DNA activates the lung endothelium and forms aggregates, a side effect linked to the transfection efficiency. In addition, the therapeutic dose-window is too narrow for any clinical application