Breaking up the correlation between efficacy and toxicity for nonviral gene delivery

Breunig, Miriam and Lungwitz, Uta and Liebl, Renate and Goepferich, Achim (2007) Breaking up the correlation between efficacy and toxicity for nonviral gene delivery. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104 (36). pp. 14454-14459. ISSN 0027-8424,

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Abstract

Nonviral nucleic acid delivery to cells and tissues is considered a standard too[ in life science research. However, although an ideal delivery system should have high efficacy and minimal toxicity, existing materials fall short, most of them being either too toxic or little effective. We hypothesized that disulficle cross-linked low-molecular-weight(MW) linear poly(ethylene imine) (MW < 4.6kDa) would overcome this limitation. Investigations with these materials revealed that the extracellular high MW provided outstandingly high transfection efficacies (up to 69.62 +/- 4.18% in HEK cells). We confirmed that the intracellular reductive degradation produced mainly nontoxic fragments (cell survival 98.69 +/- 4.79%). When we compared the polymers in > 1,400 individual experiments to seven commercial transfection reagents in seven different cell lines, we found highly superior transfection efficacies and substantially lower toxicities. This renders reductive degradation a highly promising tool for the design of new transfection materials.

Item Type: Article
Uncontrolled Keywords: MOLECULAR-WEIGHT POLYETHYLENIMINE; PERMEABILITY TRANSITION; TRANSFECTION EFFICIENCY; POTENTIAL BARRIER; MAMMALIAN-CELLS; DNA COMPLEXES; PLASMID DNA; RAT-LIVER; IN-VITRO; VECTORS; biodegradable; polyethylenimine; nucleic acid; disulfide bond; transfection
Subjects: 600 Technology > 615 Pharmacy
Divisions: Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 01 Dec 2020 11:33
Last Modified: 01 Dec 2020 11:33
URI: https://pred.uni-regensburg.de/id/eprint/32216

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