Dendrons with Spermine Surface Groups as Potential Building Blocks for Nonviral Vectors in Gene Therapy
Identifieur interne : 001C21 ( Main/Exploration ); précédent : 001C20; suivant : 001C22Dendrons with Spermine Surface Groups as Potential Building Blocks for Nonviral Vectors in Gene Therapy
Auteurs : John G. Hardy [États-Unis] ; Mauri A. Kostiainen [États-Unis] ; David K. Smith [États-Unis, Royaume-Uni] ; Nathan P. Gabrielson [États-Unis] ; Daniel W. Pack [États-Unis]Source :
- Bioconjugate Chemistry [ 1043-1802 ] ; 2005.
Abstract
This paper investigates a series of dendrons based on the Newkome dendritic scaffold that displays a naturally occurring polyamine (spermine) on their surface. These dendrons have previously been shown to interact with DNA in a generation dependent manner with the more highly branched dendrons exhibiting a strong multivalency effect for the spermine surface groups. In this paper, we investigate the ability of these dendrons to transfect DNA into cells (human breast carcinoma cells, MDA-MB-231, and murine myoblast cells, C2C12) as determined by the luciferase assay. Although the dendrons are unable to transfect DNA in their own right, they are capable of delivering DNA in vitro when administered with chloroquine, which assists with escape from endocytic vesicles. The cytotoxicity of the dendrons was determined using the XTT assay, and it was shown that the dendrons were nontoxic either alone or in the presence of DNA. However, when administered with DNA and chloroquine, the most highly branched dendron did exhibit some cytotoxicity. This paper elucidates the relationship between in vitro transfection efficiency and toxicity. While transfection efficiencies are modest, the low toxicity of the dendrons, both in their own right, and in the presence of DNA, provides encouragement that this type of building block, which has a relatively high affinity for DNA, will provide a useful starting point for the further synthetic development of more effective gene transfection agents.
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DOI: 10.1021/bc050212r
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Nonviral Vectors in Gene Therapy</title><author><name sortKey="Hardy, John G" sort="Hardy, John G" uniqKey="Hardy J" first="John G." last="Hardy">John G. Hardy</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK, andDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana Champaign,Urbana</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Kostiainen, Mauri A" sort="Kostiainen, Mauri A" uniqKey="Kostiainen M" first="Mauri A." last="Kostiainen">Mauri A. Kostiainen</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK, andDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana Champaign,Urbana</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Smith, David K" sort="Smith, David K" uniqKey="Smith D" first="David K." last="Smith">David K. Smith</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK, andDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana Champaign,Urbana</wicri:cityArea></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Royaume-Uni</country></affiliation></author><author><name sortKey="Gabrielson, Nathan P" sort="Gabrielson, Nathan P" uniqKey="Gabrielson N" first="Nathan P." last="Gabrielson">Nathan P. Gabrielson</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK, andDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana Champaign,Urbana</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Pack, Daniel W" sort="Pack, Daniel W" uniqKey="Pack D" first="Daniel W." last="Pack">Daniel W. Pack</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Illinois</region></placeName><wicri:cityArea>Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK, andDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana Champaign,Urbana</wicri:cityArea></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Bioconjugate Chemistry</title><title level="j" type="abbrev">Bioconjugate Chem.</title><idno type="ISSN">1043-1802</idno><idno type="eISSN">1520-4812</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="2005-11-04">2005</date><date when="2006-01-18">2006</date><biblScope unit="vol">17</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="172">172</biblScope><biblScope unit="page" to="178">178</biblScope></imprint><idno type="ISSN">1043-1802</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1043-1802</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">This paper investigates a series of dendrons based on the Newkome dendritic scaffold that displays a naturally occurring polyamine (spermine) on their surface. These dendrons have previously been shown to interact with DNA in a generation dependent manner with the more highly branched dendrons exhibiting a strong multivalency effect for the spermine surface groups. In this paper, we investigate the ability of these dendrons to transfect DNA into cells (human breast carcinoma cells, MDA-MB-231, and murine myoblast cells, C2C12) as determined by the luciferase assay. Although the dendrons are unable to transfect DNA in their own right, they are capable of delivering DNA in vitro when administered with chloroquine, which assists with escape from endocytic vesicles. The cytotoxicity of the dendrons was determined using the XTT assay, and it was shown that the dendrons were nontoxic either alone or in the presence of DNA. However, when administered with DNA and chloroquine, the most highly branched dendron did exhibit some cytotoxicity. This paper elucidates the relationship between in vitro transfection efficiency and toxicity. While transfection efficiencies are modest, the low toxicity of the dendrons, both in their own right, and in the presence of DNA, provides encouragement that this type of building block, which has a relatively high affinity for DNA, will provide a useful starting point for the further synthetic development of more effective gene transfection agents.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Illinois</li></region></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Hardy, John G" sort="Hardy, John G" uniqKey="Hardy J" first="John G." last="Hardy">John G. Hardy</name></region><name sortKey="Gabrielson, Nathan P" sort="Gabrielson, Nathan P" uniqKey="Gabrielson N" first="Nathan P." last="Gabrielson">Nathan P. Gabrielson</name><name sortKey="Kostiainen, Mauri A" sort="Kostiainen, Mauri A" uniqKey="Kostiainen M" first="Mauri A." last="Kostiainen">Mauri A. Kostiainen</name><name sortKey="Pack, Daniel W" sort="Pack, Daniel W" uniqKey="Pack D" first="Daniel W." last="Pack">Daniel W. Pack</name><name sortKey="Smith, David K" sort="Smith, David K" uniqKey="Smith D" first="David K." last="Smith">David K. Smith</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Smith, David K" sort="Smith, David K" uniqKey="Smith D" first="David K." last="Smith">David K. Smith</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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