New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells.

New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. Research Abstract Details 

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New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. Abstract Text:

Yemin Liu,Laura Wenning,Matthew Lynch,Theresa M Reineke,

In this report, four new poly(d-glucaramidoamine)s (1-4) have been designed to lower the toxicity of conventional polymeric nucleic acid delivery vehicles by incorporating a carbohydrate comonomer within a polyethylenimine (PEI)-like backbone. Polymers 1-4 were synthesized via polycondensation of esterified d-glucaric acid and four different amine-containing comonomers [diethylenetriamine (1), triethylenetetramine (2), tetraethylenepentamine (3), and pentaethylenehexamine (4)] in methanol. Viscometry and NMR studies suggest that the polymers are mostly linear (for 1-4, the alpha value in the Mark-Houwink-Sakurada equation = 0.6-0.7), thus indicating that polymerization occurs predominantly through the primary amines with a low degree of branching off the secondary amines. Results of gel electrophoresis shift assays show that polymers 1-4 bind pDNA at N/P ratios of 5, 3, 2, and 2, respectively. Also, dynamic light scattering and TEM experiments indicate that 1-4 compact DNA into nanoparticles (polyplexes) between 140 and 440 nm at an N/P ratio of 30. Furthermore, polyplexes formed with 1-4 deliver pDNA (plasmid DNA) containing the firefly luciferase reporter gene to BHK-21 cells in a nontoxic and highly efficient manner (as determined by luciferase gene expression). In particular, polymer 4 reveals very high delivery efficiency (equivalent to linear PEI). This result may be due in part to the "proton sponge" hypothesis proposed by Behr et al. Polymers containing amines that are protonated in the endosomal pH range (between about 7.4-5.0) reveal enhanced gene delivery profiles.

New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. Publishing Authors By Initials

Y Liu,L Wenning,M Lynch,TM Reineke,

For similar genetic structures: plasmids research abstracts see: genetic structures: plasmids research

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New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of the American Chemical Society

VOLUME: 126

Page Numbers: 7422-3

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 23

MONTH: Jun

YEAR: 2004

New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. Information

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LANGUAGE: eng

NlmUniqueID: 7503056

New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. Keywords Mesh Terms:

KEYWORDS: Plasmids

MESH TERMS: genetics

Chemical & Substance for Abstract: New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells.

AFFILIATION: Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221-0172, USA.

Country: United States

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MEDLINETA: J Am Chem Soc

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