DOI: 10.1073/pnas.98.3.1200. Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini

Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini

10.1073/pnas.98.3.1200

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Protein expression after delivery of plasmid DNA to the cell nucleus depends on the processes of transcription and translation. Cytotoxic gene-delivery systems may compromise these processes and limit protein expression. This situation is perhaps most prevalent in current nonviral polycationic gene-delivery systems in which the polycationic nature of the delivery system can lead to cytotoxicity. To approach the problem of creating nontoxic but effective gene-delivery systems, we hypothesized that by optimizing the balance between polymer cationic density with endosomal escape moieties, effective gene transfer with low cytotoxicity could be created. As a model system, we synthesized a series of polymers whose side-chain termini varied with respect to the balance of cationic centers and endosomal escape moieties. Specifically, by polymer-analogous amidation we conjugated imidazole groups to the ɛ-amines of polylysine in varying mole ratios (73.5 mol % imidazole, 82.5 mol % imidazole, and 86.5 mol % imidazole). The primary ɛ-amine terminus of polylysine served as a model for the cationic centers, whereas the imidazole groups served as a model for the endosomal escape moieties. These polymers condensed plasmid DNA into nanostructures <150 nm and possessed little cytotoxicityin vitro. Transfection efficiency, as measured by luciferase protein expression, increased with increasing imidazole content of the polymers in a nonlinear relationship. The polymer with the highest imidazole content (86.5 mol %) mediated the highest protein expression, with levels equal to those mediated by polyethylenimine, but with little to no cytotoxicity.

Bibliography

Putnam, D., Gentry, C. A., Pack, D. W., & Langer, R. (2001). Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini. Proceedings of the National Academy of Sciences, 98(3), 1200â1205.

Authors 4

David Putnam (first)
Christine A. Gentry (additional)
Daniel W. Pack (additional)
Robert Langer (additional)

References 42 Referenced 374

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Dates

Type	When
Created	13 years, 1 month ago (July 26, 2012, 7:06 p.m.)
Deposited	1 year, 4 months ago (April 27, 2024, 10:25 a.m.)
Indexed	5 days, 10 hours ago (Aug. 27, 2025, 11:35 a.m.)
Issued	24 years, 7 months ago (Jan. 23, 2001)
Published	24 years, 7 months ago (Jan. 23, 2001)
Published Online	24 years, 7 months ago (Jan. 23, 2001)
Published Print	24 years, 7 months ago (Jan. 30, 2001)

Funders 0

None

BibTeX

@article{Putnam_2001, title={Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.98.3.1200}, DOI={10.1073/pnas.98.3.1200}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Putnam, David and Gentry, Christine A. and Pack, Daniel W. and Langer, Robert}, year={2001}, month=jan, pages={1200–1205} }

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