US EPA

4395927 

Journal Article 

Genuine DNA/polyethylenimine (PEI) complexes improve transfection properties and cell survival 

Erbacher, P; Bettinger, T; Brion, E; Coll, JL; Plank, C; Behr, JP; Remy, JS 

2004 

Yes 

Journal of Drug Targeting
ISSN: 1061-186X 

12 

4 

223-236 

English 

15506171 

10.1080/10611860410001723487 

WOS:000223126800006 

Polyethylenimine (PEI) has been described as one of the most efficient cationic polymers for in vitro gene delivery. Systemic delivery of PEI/DNA polyplexes leads to a lung-expression tropism. Selective in vivo gene transfer would require targeting and stealth particles. Here, we describe two strategies for chemically coupling polyethylene glycol (PEG) to PEI, to form protected ligand-bearing particles. Pre-grafted PEG-PEI polymers lost their DNA condensing property, hence their poor performances. Coupling PEG to pre-formed PEI/DNA particles led to the expected physical properties. However, low transfection efficacies raised the question of the fate of excess free polymer in solution. We have developed a straightforward a purification assay, which uses centrifugation-based ultrafiltration. Crude polyplexes were purified, with up to 60% of the initial PEI dose being removed. The resulting purified and unshielded PEI/DNA polyplexes are more efficient for transfection and less toxic to cells in culture than the crude ones. Moreover, the in vivo toxicity of the polyplexes was greatly reduced, without affecting their efficacy.