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Novel vectors for gene delivery formed by self-assembly of DNA with poly(l-lysine) grafted with hydrophilic polymers

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Novel vectors for gene delivery formed by self-assembly of DNA with poly(l-lysine) grafted with hydrophilic polymers

Auteurs : Veska Toncheva [Belgique] ; Margreet A. Wolfert [Royaume-Uni] ; Philip R. Dash [Royaume-Uni] ; David Oupicky [République tchèque] ; Karel Ulbrich [République tchèque] ; Leonard W. Seymour [Royaume-Uni] ; Etienne H. Schacht [Belgique]

Source :

BBA - General Subjects [ 0304-4165 ] ; 1998.

RBID : ISTEX:859A814AE42B0EC5A06BCD133CF8499438E10BB3

English descriptors

Teeft :
- Acta, Agarose, Aldrich chemical, Amino functions, Aqueous solubility, Atomic force, Atomic force microscopy, Average diameter, Bicinconninic acid, Biochimica, Biological properties, Biophysica, Biophysica acta, Block copolymers, Bromide, Calcium hydride, Calf thymus, Cationic, Cationic polymer, Cationic polymers, Cell lysates, Charge neutrality, Charge ratio, Charge ratios, Citric acid, Copolymer, Cytotoxicity, Czech republic, Dextran, Different charge ratios, Discrete complexes, Dnarethidium bromide fluorescence, Effective shielding, Error bars, Ethidium, Ethidium bromide, Ethidium bromiderdna fluorescence, Ethylene glycol, Ethylene oxide, Expression vector, Free polymers, Gene delivery, Gene expression, Gene therapy, Gene transfer, Grafted, Grafted copolymer, Grafted copolymerrdna complexes, Grafted copolymers, Grafted polymer, Grafted polymers, Greater cytotoxicity, Greater transfection, Grml, Higher charge ratios, Hydrophilic, Hydrophilic block, Hydrophilic blocks, Hydrophilic polymer, Hydrophilic polymer blocks, Intravenous administration, Lysis buffer, Membrane activity, Methylene chloride, Molecular weight, Phpma, Pllrdna, Polyelectrolyte, Polyelectrolyte complexes, Polyelectrolyte interaction, Polymer, Polymerrdna complexes, Positive charge, Reaction mixture, Remote sites, Room temperature, Sigma chemical, Simple pllrdna complexes, Solubility, Spontaneous transfection, Substitution, Succinic anhydride, Surface charge, Total protein content, Transfection, Unpublished data, Various concentrations, Water solubility, Weight characteristics, Zeta.

Abstract

Abstract: Complexes formed between DNA and cationic polymers are attracting increasing attention as novel synthetic vectors for delivery of genes. We are trying to improve biological properties of such complexes by oriented self-assembly of DNA with cationic-hydrophilic block copolymers, designed to enshroud the complex within a protective hydrophilic polymer corona. Poly(l-lysine) (pLL) grafted with range of hydrophilic polymer blocks, including poly(ethylene glycol) (pEG), dextran and poly[N-(2-hydroxypropyl)methacrylamide] (pHPMA), shows efficient binding to DNA and mediates particle self-assembly and inhibition of ethidium bromide/DNA fluorescence. The complexes formed are discrete and typically about 100 nm diameter, viewed by atomic force microscopy. Surface charges are slightly shielded by the presence of the hydrophilic polymer, and complexes generally show decreased cytotoxicity compared with simple pLL/DNA complexes. pEG-containing complexes show increased transfection activity against cells in vitro. Complexes formed with all polymer conjugates showed greater aqueous solubility than simple pLL/DNA complexes, particularly at charge neutrality. These materials appear to have the ability to regulate the physicochemical and biological properties of polycation/DNA complexes, and should find important applications in packaging of nucleic acids for specific biological applications.

Url:

https://api.istex.fr/ark:/67375/6H6-DPKFJMHK-F/fulltext.pdf

DOI: 10.1016/S0304-4165(98)00004-X

Affiliations:

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<profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acta</term>
<term>Agarose</term>
<term>Aldrich chemical</term>
<term>Amino functions</term>
<term>Aqueous solubility</term>
<term>Atomic force</term>
<term>Atomic force microscopy</term>
<term>Average diameter</term>
<term>Bicinconninic acid</term>
<term>Biochimica</term>
<term>Biological properties</term>
<term>Biophysica</term>
<term>Biophysica acta</term>
<term>Block copolymers</term>
<term>Bromide</term>
<term>Calcium hydride</term>
<term>Calf thymus</term>
<term>Cationic</term>
<term>Cationic polymer</term>
<term>Cationic polymers</term>
<term>Cell lysates</term>
<term>Charge neutrality</term>
<term>Charge ratio</term>
<term>Charge ratios</term>
<term>Citric acid</term>
<term>Copolymer</term>
<term>Cytotoxicity</term>
<term>Czech republic</term>
<term>Dextran</term>
<term>Different charge ratios</term>
<term>Discrete complexes</term>
<term>Dnarethidium bromide fluorescence</term>
<term>Effective shielding</term>
<term>Error bars</term>
<term>Ethidium</term>
<term>Ethidium bromide</term>
<term>Ethidium bromiderdna fluorescence</term>
<term>Ethylene glycol</term>
<term>Ethylene oxide</term>
<term>Expression vector</term>
<term>Free polymers</term>
<term>Gene delivery</term>
<term>Gene expression</term>
<term>Gene therapy</term>
<term>Gene transfer</term>
<term>Grafted</term>
<term>Grafted copolymer</term>
<term>Grafted copolymerrdna complexes</term>
<term>Grafted copolymers</term>
<term>Grafted polymer</term>
<term>Grafted polymers</term>
<term>Greater cytotoxicity</term>
<term>Greater transfection</term>
<term>Grml</term>
<term>Higher charge ratios</term>
<term>Hydrophilic</term>
<term>Hydrophilic block</term>
<term>Hydrophilic blocks</term>
<term>Hydrophilic polymer</term>
<term>Hydrophilic polymer blocks</term>
<term>Intravenous administration</term>
<term>Lysis buffer</term>
<term>Membrane activity</term>
<term>Methylene chloride</term>
<term>Molecular weight</term>
<term>Phpma</term>
<term>Pllrdna</term>
<term>Polyelectrolyte</term>
<term>Polyelectrolyte complexes</term>
<term>Polyelectrolyte interaction</term>
<term>Polymer</term>
<term>Polymerrdna complexes</term>
<term>Positive charge</term>
<term>Reaction mixture</term>
<term>Remote sites</term>
<term>Room temperature</term>
<term>Sigma chemical</term>
<term>Simple pllrdna complexes</term>
<term>Solubility</term>
<term>Spontaneous transfection</term>
<term>Substitution</term>
<term>Succinic anhydride</term>
<term>Surface charge</term>
<term>Total protein content</term>
<term>Transfection</term>
<term>Unpublished data</term>
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<front><div type="abstract" xml:lang="en">Abstract: Complexes formed between DNA and cationic polymers are attracting increasing attention as novel synthetic vectors for delivery of genes. We are trying to improve biological properties of such complexes by oriented self-assembly of DNA with cationic-hydrophilic block copolymers, designed to enshroud the complex within a protective hydrophilic polymer corona. Poly(l-lysine) (pLL) grafted with range of hydrophilic polymer blocks, including poly(ethylene glycol) (pEG), dextran and poly[N-(2-hydroxypropyl)methacrylamide] (pHPMA), shows efficient binding to DNA and mediates particle self-assembly and inhibition of ethidium bromide/DNA fluorescence. The complexes formed are discrete and typically about 100 nm diameter, viewed by atomic force microscopy. Surface charges are slightly shielded by the presence of the hydrophilic polymer, and complexes generally show decreased cytotoxicity compared with simple pLL/DNA complexes. pEG-containing complexes show increased transfection activity against cells in vitro. Complexes formed with all polymer conjugates showed greater aqueous solubility than simple pLL/DNA complexes, particularly at charge neutrality. These materials appear to have the ability to regulate the physicochemical and biological properties of polycation/DNA complexes, and should find important applications in packaging of nucleic acids for specific biological applications.</div>
</front>
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Novel vectors for gene delivery formed by self-assembly of DNA with poly(l-lysine) grafted with hydrophilic polymers

Novel vectors for gene delivery formed by self-assembly of DNA with poly(l-lysine) grafted with hydrophilic polymers

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English descriptors

Abstract

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