Intranasal administration of plasmid DNA nanoparticles yields successful transfection and expression of a reporter protein in rat brain.
Identifieur interne : 001C14 ( Main/Exploration ); précédent : 001C13; suivant : 001C15Intranasal administration of plasmid DNA nanoparticles yields successful transfection and expression of a reporter protein in rat brain.
Auteurs : B T Harmon [États-Unis] ; A E Aly [États-Unis] ; L. Padegimas [États-Unis] ; O. Sesenoglu-Laird [États-Unis] ; M J Cooper [États-Unis] ; B L Waszczak [États-Unis]Source :
- Gene therapy [ 1476-5462 ] ; 2014.
Descripteurs français
- KwdFr :
- ADN circulaire (administration et posologie), Administration par voie nasale, Animaux, Barrière hémato-encéphalique, Encéphale (physiologie), Expression des gènes, Gènes rapporteurs, Mâle, Nanoparticules (administration et posologie), Plasmides (administration et posologie), Protéines à fluorescence verte (administration et posologie), Protéines à fluorescence verte (génétique), Rat Sprague-Dawley, Rats, Thérapie génétique (), Transfection (), Vecteurs génétiques.
- MESH :
- administration et posologie : ADN circulaire, Nanoparticules, Plasmides, Protéines à fluorescence verte.
- génétique : Protéines à fluorescence verte.
- physiologie : Encéphale.
- Administration par voie nasale, Animaux, Barrière hémato-encéphalique, Expression des gènes, Gènes rapporteurs, Mâle, Rat Sprague-Dawley, Rats, Thérapie génétique, Transfection, Vecteurs génétiques.
English descriptors
- KwdEn :
- Administration, Intranasal, Animals, Blood-Brain Barrier, Brain (physiology), DNA, Circular (administration & dosage), Gene Expression, Genes, Reporter, Genetic Therapy (methods), Genetic Vectors, Green Fluorescent Proteins (administration & dosage), Green Fluorescent Proteins (genetics), Male, Nanoparticles (administration & dosage), Plasmids (administration & dosage), Rats, Rats, Sprague-Dawley, Transfection (methods).
- MESH :
- chemical , administration & dosage : DNA, Circular, Green Fluorescent Proteins.
- chemical , genetics : Green Fluorescent Proteins.
- administration & dosage : Nanoparticles, Plasmids.
- methods : Genetic Therapy, Transfection.
- physiology : Brain.
- Administration, Intranasal, Animals, Blood-Brain Barrier, Gene Expression, Genes, Reporter, Genetic Vectors, Male, Rats, Rats, Sprague-Dawley.
Abstract
Viral vectors are a commonly used method for gene therapy because of their highly efficient transduction of cells. However, many vectors have a small genetic capacity, and their potential for immunogenicity can limit their usefulness. Moreover, for disorders of the central nervous system (CNS), the need for invasive surgical delivery of viruses to the brain also detracts from their clinical applicability. Here, we show that intranasal delivery of unimolecularly compacted DNA nanoparticles (DNA NPs), which consist of single molecules of plasmid DNA encoding enhanced green fluorescent protein (eGFP) compacted with 10 kDa polyethylene glycol (PEG)-substituted lysine 30-mers (CK30PEG10k), successfully transfect cells in the rat brain. Direct eGFP fluorescence microscopy, eGFP-immunohistochemistry (IHC) and eGFP-ELISA all demonstrated eGFP protein expression 2 days after intranasal delivery. eGFP-positive cells were found throughout the rostral-caudal axis of the brain, most often adjacent to capillary endothelial cells. This localization provides evidence for distribution of the nasally administered DNA NPs via perivascular flow. These results are the first report that intranasal delivery of DNA NPs can bypass the blood-brain barrier and transfect and express the encoded protein in the rat brain, affording a non-invasive approach for gene therapy of CNS disorders.
DOI: 10.1038/gt.2014.28
PubMed: 24670994
Affiliations:
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Sesenoglu-Laird</name><affiliation wicri:level="2"><nlm:affiliation>Copernicus Therapeutics, Inc., Cleveland, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Copernicus Therapeutics, Inc., Cleveland, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Cooper, M J" sort="Cooper, M J" uniqKey="Cooper M" first="M J" last="Cooper">M J Cooper</name><affiliation wicri:level="2"><nlm:affiliation>Copernicus Therapeutics, Inc., Cleveland, OH, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Copernicus Therapeutics, Inc., Cleveland, OH</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Waszczak, B L" sort="Waszczak, B L" uniqKey="Waszczak B" first="B L" last="Waszczak">B L Waszczak</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, Northeastern University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></analytic><series><title level="j">Gene therapy</title><idno type="eISSN">1476-5462</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Intranasal</term><term>Animals</term><term>Blood-Brain Barrier</term><term>Brain (physiology)</term><term>DNA, Circular (administration & dosage)</term><term>Gene Expression</term><term>Genes, Reporter</term><term>Genetic Therapy (methods)</term><term>Genetic Vectors</term><term>Green Fluorescent Proteins (administration & dosage)</term><term>Green Fluorescent Proteins (genetics)</term><term>Male</term><term>Nanoparticles (administration & dosage)</term><term>Plasmids (administration & dosage)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Transfection (methods)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN circulaire (administration et posologie)</term><term>Administration par voie nasale</term><term>Animaux</term><term>Barrière hémato-encéphalique</term><term>Encéphale (physiologie)</term><term>Expression des gènes</term><term>Gènes rapporteurs</term><term>Mâle</term><term>Nanoparticules (administration et posologie)</term><term>Plasmides (administration et posologie)</term><term>Protéines à fluorescence verte (administration et posologie)</term><term>Protéines à fluorescence verte (génétique)</term><term>Rat Sprague-Dawley</term><term>Rats</term><term>Thérapie génétique ()</term><term>Transfection ()</term><term>Vecteurs génétiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>DNA, Circular</term><term>Green Fluorescent Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Green Fluorescent Proteins</term></keywords><keywords scheme="MESH" qualifier="administration & dosage" xml:lang="en"><term>Nanoparticles</term><term>Plasmids</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>ADN circulaire</term><term>Nanoparticules</term><term>Plasmides</term><term>Protéines à fluorescence verte</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines à fluorescence verte</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genetic Therapy</term><term>Transfection</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Encéphale</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Intranasal</term><term>Animals</term><term>Blood-Brain Barrier</term><term>Gene Expression</term><term>Genes, Reporter</term><term>Genetic Vectors</term><term>Male</term><term>Rats</term><term>Rats, Sprague-Dawley</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Administration par voie nasale</term><term>Animaux</term><term>Barrière hémato-encéphalique</term><term>Expression des gènes</term><term>Gènes rapporteurs</term><term>Mâle</term><term>Rat Sprague-Dawley</term><term>Rats</term><term>Thérapie génétique</term><term>Transfection</term><term>Vecteurs génétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Viral vectors are a commonly used method for gene therapy because of their highly efficient transduction of cells. However, many vectors have a small genetic capacity, and their potential for immunogenicity can limit their usefulness. Moreover, for disorders of the central nervous system (CNS), the need for invasive surgical delivery of viruses to the brain also detracts from their clinical applicability. Here, we show that intranasal delivery of unimolecularly compacted DNA nanoparticles (DNA NPs), which consist of single molecules of plasmid DNA encoding enhanced green fluorescent protein (eGFP) compacted with 10 kDa polyethylene glycol (PEG)-substituted lysine 30-mers (CK30PEG10k), successfully transfect cells in the rat brain. Direct eGFP fluorescence microscopy, eGFP-immunohistochemistry (IHC) and eGFP-ELISA all demonstrated eGFP protein expression 2 days after intranasal delivery. eGFP-positive cells were found throughout the rostral-caudal axis of the brain, most often adjacent to capillary endothelial cells. This localization provides evidence for distribution of the nasally administered DNA NPs via perivascular flow. These results are the first report that intranasal delivery of DNA NPs can bypass the blood-brain barrier and transfect and express the encoded protein in the rat brain, affording a non-invasive approach for gene therapy of CNS disorders.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Massachusetts</li><li>Ohio</li></region></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Harmon, B T" sort="Harmon, B T" uniqKey="Harmon B" first="B T" last="Harmon">B T Harmon</name></region><name sortKey="Aly, A E" sort="Aly, A E" uniqKey="Aly A" first="A E" last="Aly">A E Aly</name><name sortKey="Cooper, M J" sort="Cooper, M J" uniqKey="Cooper M" first="M J" last="Cooper">M J Cooper</name><name sortKey="Padegimas, L" sort="Padegimas, L" uniqKey="Padegimas L" first="L" last="Padegimas">L. Padegimas</name><name sortKey="Sesenoglu Laird, O" sort="Sesenoglu Laird, O" uniqKey="Sesenoglu Laird O" first="O" last="Sesenoglu-Laird">O. Sesenoglu-Laird</name><name sortKey="Waszczak, B L" sort="Waszczak, B L" uniqKey="Waszczak B" first="B L" last="Waszczak">B L Waszczak</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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