Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 36, Pages 14454-14459Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0703882104
Keywords
biodegradable; polyethylenimine; nucleic acid; disulfide bond; transfection
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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.
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