Regional hydrodynamic gene delivery to the rat liver with physiological volumes of DNA solution
Identifieur interne : 001F59 ( Main/Exploration ); précédent : 001F58; suivant : 001F60Regional hydrodynamic gene delivery to the rat liver with physiological volumes of DNA solution
Auteurs : Xiaohong Zhang [Royaume-Uni] ; Xuebin Dong [Royaume-Uni] ; Greta J. Sawyer [Royaume-Uni] ; Louise Collins [Royaume-Uni] ; John W. Fabre [Royaume-Uni]Source :
- The Journal of Gene Medicine [ 1099-498X ] ; 2004-06.
English descriptors
- Teeft :
- Aspartate transaminase, Budker, Cava, Cellular entry, Chloroquine, Clinical application, Clinical practice, Copyright, Endocytic, Experimental model, Fabre, Gene, Gene delivery, Gene expression, Gene therapy, Gene transfer, Hepatic, Hepatic artery, Hepatic veins, Hydrodynamic, Hydrodynamic gene delivery, Individual lobes, Individual rats, Inferior vena cava, Isotonic solutions, John wiley sons, Large volumes, Ligature, Liquid nitrogen, Liver, Liver enzymes, Liver lobe, Liver mass, Liver weight, Lobe, Luciferase, Luciferase activity, Median lobe, Naked plasmid, Nanoparticles, Obstruction, Peptide, Perfusion, Pgl3, Pgl3 plasmid, Plasmid, Portal, Portal vein, Rat, Regional hydrodynamic gene delivery, Retrograde gene delivery, Small volumes, Standard protocol, Synthetic peptide vector system, Systemic, Systemic chloroquine, Systemic vein, Transplantation, Vena, Vena cava, Zhang.
Abstract
Background: The major barrier to the clinical application of hydrodynamic gene delivery to the liver is the large volume of fluid required using standard protocols. Regional hydrodynamic gene delivery via branches of the portal vein has not previously been reported, and we have evaluated this approach in a rat model. Methods: The pGL3 plasmid with the luciferase reporter gene was used at 50 µg/ml in isotonic solutions, and was administered with a syringe pump for precise control of the hydrodynamic conditions evaluated. Gene expression was individually measured in six anatomically distinct liver lobes. The effect of systemic chloroquine to promote endocytic escape and a (Lys)16‐containing peptide to condense the DNA into ∼100‐nm nanoparticles was also evaluated. Results: Hydrodynamic conditions for excellent gene delivery were obtained by using 3‐ml volumes (∼12 ml/kg) of isotonic DNA solution delivered at 24 ml/min to the right lateral lobe (∼20% of the liver mass). Under these conditions, >95% of gene delivery usually occurred in the targeted right lateral lobe. Outflow obstruction was essential for gene delivery, both at optimal and at very low levels of hydrodynamic gene delivery. The use of systemic chloroquine to promote endocytic escape did not augment hydrodynamic gene delivery, while condensation of DNA in non‐ionic isotonic solutions (5% dextrose) to nanoparticles of ∼100 nm completely abolished gene delivery. Conclusions: Regional hydrodynamic gene delivery via a branch of the portal vein offers a physiological model of liver gene therapy, for experimental and clinical application. Copyright © 2004 John Wiley & Sons, Ltd.
Url:
DOI: 10.1002/jgm.595
Affiliations:
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Sawyer</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Clinical Sciences, Guy's, King's & St Thomas' School of Medicine, The Rayne Institute, King's Denmark Hill Campus, 123 Coldharbour Lane, London SE5 9NU</wicri:regionArea><wicri:noRegion>London SE5 9NU</wicri:noRegion></affiliation></author><author><name sortKey="Collins, Louise" sort="Collins, Louise" uniqKey="Collins L" first="Louise" last="Collins">Louise Collins</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Clinical Sciences, Guy's, King's & St Thomas' School of Medicine, The Rayne Institute, King's Denmark Hill Campus, 123 Coldharbour Lane, London SE5 9NU</wicri:regionArea><wicri:noRegion>London SE5 9NU</wicri:noRegion></affiliation></author><author><name sortKey="Fabre, John W" sort="Fabre, John W" uniqKey="Fabre J" first="John W." last="Fabre">John W. Fabre</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Clinical Sciences, Guy's, King's & St Thomas' School of Medicine, The Rayne Institute, King's Denmark Hill Campus, 123 Coldharbour Lane, London SE5 9NU</wicri:regionArea><wicri:noRegion>London SE5 9NU</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Royaume-Uni</country></affiliation><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Correspondence address: Department of Clinical Sciences, Guy's, King's & St Thomas' School of Medicine, The Rayne Institute, King's Denmark Hill Campus, 123 Coldharbour Lane, London SE5 9NU</wicri:regionArea><wicri:noRegion>London SE5 9NU</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Gene Medicine</title><title level="j" type="alt">JOURNAL OF GENE MEDICINE, THE</title><idno type="ISSN">1099-498X</idno><idno type="eISSN">1521-2254</idno><imprint><biblScope unit="vol">6</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="693">693</biblScope><biblScope unit="page" to="703">703</biblScope><biblScope unit="page-count">11</biblScope><publisher>John Wiley & Sons, Ltd.</publisher><pubPlace>Chichester, UK</pubPlace><date type="published" when="2004-06">2004-06</date></imprint><idno type="ISSN">1099-498X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1099-498X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Aspartate transaminase</term><term>Budker</term><term>Cava</term><term>Cellular entry</term><term>Chloroquine</term><term>Clinical application</term><term>Clinical practice</term><term>Copyright</term><term>Endocytic</term><term>Experimental model</term><term>Fabre</term><term>Gene</term><term>Gene delivery</term><term>Gene expression</term><term>Gene therapy</term><term>Gene transfer</term><term>Hepatic</term><term>Hepatic artery</term><term>Hepatic veins</term><term>Hydrodynamic</term><term>Hydrodynamic gene delivery</term><term>Individual lobes</term><term>Individual rats</term><term>Inferior vena cava</term><term>Isotonic solutions</term><term>John wiley sons</term><term>Large volumes</term><term>Ligature</term><term>Liquid nitrogen</term><term>Liver</term><term>Liver enzymes</term><term>Liver lobe</term><term>Liver mass</term><term>Liver weight</term><term>Lobe</term><term>Luciferase</term><term>Luciferase activity</term><term>Median lobe</term><term>Naked plasmid</term><term>Nanoparticles</term><term>Obstruction</term><term>Peptide</term><term>Perfusion</term><term>Pgl3</term><term>Pgl3 plasmid</term><term>Plasmid</term><term>Portal</term><term>Portal vein</term><term>Rat</term><term>Regional hydrodynamic gene delivery</term><term>Retrograde gene delivery</term><term>Small volumes</term><term>Standard protocol</term><term>Synthetic peptide vector system</term><term>Systemic</term><term>Systemic chloroquine</term><term>Systemic vein</term><term>Transplantation</term><term>Vena</term><term>Vena cava</term><term>Zhang</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: The major barrier to the clinical application of hydrodynamic gene delivery to the liver is the large volume of fluid required using standard protocols. Regional hydrodynamic gene delivery via branches of the portal vein has not previously been reported, and we have evaluated this approach in a rat model. Methods: The pGL3 plasmid with the luciferase reporter gene was used at 50 µg/ml in isotonic solutions, and was administered with a syringe pump for precise control of the hydrodynamic conditions evaluated. Gene expression was individually measured in six anatomically distinct liver lobes. The effect of systemic chloroquine to promote endocytic escape and a (Lys)16‐containing peptide to condense the DNA into ∼100‐nm nanoparticles was also evaluated. Results: Hydrodynamic conditions for excellent gene delivery were obtained by using 3‐ml volumes (∼12 ml/kg) of isotonic DNA solution delivered at 24 ml/min to the right lateral lobe (∼20% of the liver mass). Under these conditions, >95% of gene delivery usually occurred in the targeted right lateral lobe. Outflow obstruction was essential for gene delivery, both at optimal and at very low levels of hydrodynamic gene delivery. The use of systemic chloroquine to promote endocytic escape did not augment hydrodynamic gene delivery, while condensation of DNA in non‐ionic isotonic solutions (5% dextrose) to nanoparticles of ∼100 nm completely abolished gene delivery. Conclusions: Regional hydrodynamic gene delivery via a branch of the portal vein offers a physiological model of liver gene therapy, for experimental and clinical application. Copyright © 2004 John Wiley & Sons, Ltd.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Zhang, Xiaohong" sort="Zhang, Xiaohong" uniqKey="Zhang X" first="Xiaohong" last="Zhang">Xiaohong Zhang</name></noRegion><name sortKey="Collins, Louise" sort="Collins, Louise" uniqKey="Collins L" first="Louise" last="Collins">Louise Collins</name><name sortKey="Dong, Xuebin" sort="Dong, Xuebin" uniqKey="Dong X" first="Xuebin" last="Dong">Xuebin Dong</name><name sortKey="Fabre, John W" sort="Fabre, John W" uniqKey="Fabre J" first="John W." last="Fabre">John W. Fabre</name><name sortKey="Fabre, John W" sort="Fabre, John W" uniqKey="Fabre J" first="John W." last="Fabre">John W. Fabre</name><name sortKey="Fabre, John W" sort="Fabre, John W" uniqKey="Fabre J" first="John W." last="Fabre">John W. Fabre</name><name sortKey="Sawyer, Greta J" sort="Sawyer, Greta J" uniqKey="Sawyer G" first="Greta J." last="Sawyer">Greta J. Sawyer</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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