| Association and dissociation characteristics of polymer/DNA complexes used for gene delivery. | |
| | |
MedLine Citation:
|
PMID: 10554094 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
PURPOSE: The DNA association/dissociation properties of water-soluble cationic methacrylate polymers with closely related structures (poly(2-dimethylamino)ethyl methacrylate) [p(DMAEMA)], poly(2-(trimethylamino)ethyl methacrylate chloride) [p(TMAEMA)]) and the frequently used transfectant poly(L-lysine) were studied to gain a better insight into their transfection characteristics. METHODS: Association of DNA with different polymers and dissociation of the complexes, achieved by adding an excess of anionic polymers or salt, were studied by using spectroscopic techniques (fluorescence, circular dichroism (CD)), agarose gel electrophoresis and an enzymatic assay (DNase I treatment). The transfection efficiency of the polyplexes was evaluated in tissue culture with OVCAR-3 cells. RESULTS: Plasmid DNA complexed with either poly(L-lysine) or p(DMAEMA) was protected against digestion by DNase I. Fluorescence and CD spectroscopy as well as gel electrophoresis revealed that p(DMAEMA) with a relatively high molecular weight and poly(L-lysine) have similar DNA association/dissociation characteristics. Therefore, differences in transfection potential of the polyplexes cannot be ascribed to differences in binding characteristics, but are probably caused by other factors. As compared with the other polymers, p(TMAEMA) has a high affinity for DNA as was concluded from the observation that poly(aspartic acid) was unable to fully dissociate complexes containing this polymer. This fact might very well explain the low transfection efficiency of these polyplexes. p(DMAEMA) with a relatively low molecular weight probably has a low affinity for DNA, which might explain both the formation of DNA aggregates (psi-DNA) and the low transfection potential obtained when using this polymer. CONCLUSIONS: DNA association/dissociation studies shed light on the preferred characteristics of polymeric transfectants. |
| | |
Authors:
|
C Arigita; N J Zuidam; D J Crommelin; W E Hennink |
Related Documents
:
|
16869554 - Plasmid dna encapsulation within cationic diblock copolymer vesicles for gene delivery. 12101434 - Characterization of poly((n-trimethylammonium) ethyl methacrylate)-based gene delivery ... 12204334 - Endocytosis is involved in dna uptake in yeast. 3663224 - Plasmid dna adsorbed to ph-sensitive liposomes efficiently transforms the target cells. 776974 - Selective inhibition of the dnase activity of the recbc enzyme by the dna binding prote... 15486204 - Differential recognition by the tumor suppressor protein p53 of dna modified by the nov... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Pharmaceutical research Volume: 16 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 1999 Oct |
Date Detail:
|
Created Date: 1999-12-23 Completed Date: 1999-12-23 Revised Date: 2000-12-18 |
Medline Journal Info:
|
Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 1534-41 Citation Subset: IM |
Affiliation:
|
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Faculty of Pharmacy, Utrecht University, The Netherlands. c.arigita@pharm.uu.nl |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Survival Cells, Cultured Circular Dichroism DNA / administration & dosage*, analysis Electrophoresis, Agar Gel Gene Transfer Techniques* Methacrylates / chemistry Molecular Weight Polylysine Polymers Spectrometry, Fluorescence Transfection |
| Chemical | |
Reg. No./Substance:
|
0/Methacrylates; 0/Polymers; 0/poly(2-(trimethylamino)ethyl methacrylate); 25104-18-1/Polylysine; 2867-47-2/2-(dimethylamino)ethyl methacrylate; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prodrug approach for alphaIIbbeta3-peptidomimetic antagonists to enhance their transport in monolaye...
Next Document: Distribution of a 20-mer phosphorothioate oligonucleotide, CGP69846A (ISIS 5132), into airway leukoc...