Gene Delivery Using Polymer Therapeutics
Identifieur interne : 001D27 ( Main/Exploration ); précédent : 001D26; suivant : 001D28Gene Delivery Using Polymer Therapeutics
Auteurs : Ernst Wagner [Allemagne] ; Julia Kloeckner [Allemagne]Source :
- Advances in Polymer Science [ 0065-3195 ]
Abstract
Abstract: The use of polymers as synthetic non-viral carriers for introducing nucleic acids into cells appears very appealing. Polymers can be generated in large quantities in chemically defined, non-antigenic and non-immunogenic form. A plethora of different chemical structures and polymer sizes may be applied to tailor-made polymers with optimized characteristics for the extracellular delivery of nucleic acid to the target tissue and the subsequent intracellular delivery into the target cells. For the purpose of nucleic acid transfer, polymers have been applied for incorporating nucleic acids into nanoparticles or microspheres. Alternatively, cationic polymers are applied as carriers for complexing gene vectors into polyplexes. Polyplexes form spontaneously upon mixing negatively charged nucleic acid with the polycationic polymer due to electrostatic interaction. This process can be controlled to result in the formation of particles with defined virus-like sizes which efficiently transfect cell cultures and also have shown encouraging gene transfer potential in in vivo administration. With first-generation polymeric carriers, gene therapeutic effects have been demonstrated in animals, although modest efficiencies and significant toxicity restrict broader therapeutic application. Key issues for future optimization of polyplexes include improved specificity for the target tissue, enhanced intracellular uptake, and reduced toxicity and immunogenicity. Novel cationic polymers have to be made more biocompatible by reducing their potential for unspecific adverse interactions with the host, and by designing them in a biodegradable form. “Smart” polymers and polymer conjugates are being developed that in a dynamic manner present virus-like delivery functions in the appropriate phase of the gene delivery process.
Url:
DOI: 10.1007/12_023
Affiliations:
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Polymers can be generated in large quantities in chemically defined, non-antigenic and non-immunogenic form. A plethora of different chemical structures and polymer sizes may be applied to tailor-made polymers with optimized characteristics for the extracellular delivery of nucleic acid to the target tissue and the subsequent intracellular delivery into the target cells. For the purpose of nucleic acid transfer, polymers have been applied for incorporating nucleic acids into nanoparticles or microspheres. Alternatively, cationic polymers are applied as carriers for complexing gene vectors into polyplexes. Polyplexes form spontaneously upon mixing negatively charged nucleic acid with the polycationic polymer due to electrostatic interaction. This process can be controlled to result in the formation of particles with defined virus-like sizes which efficiently transfect cell cultures and also have shown encouraging gene transfer potential in in vivo administration. With first-generation polymeric carriers, gene therapeutic effects have been demonstrated in animals, although modest efficiencies and significant toxicity restrict broader therapeutic application. Key issues for future optimization of polyplexes include improved specificity for the target tissue, enhanced intracellular uptake, and reduced toxicity and immunogenicity. Novel cationic polymers have to be made more biocompatible by reducing their potential for unspecific adverse interactions with the host, and by designing them in a biodegradable form. “Smart” polymers and polymer conjugates are being developed that in a dynamic manner present virus-like delivery functions in the appropriate phase of the gene delivery process.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Bavière</li><li>District de Haute-Bavière</li></region><settlement><li>Munich</li></settlement></list><tree><country name="Allemagne"><region name="Bavière"><name sortKey="Wagner, Ernst" sort="Wagner, Ernst" uniqKey="Wagner E" first="Ernst" last="Wagner">Ernst Wagner</name></region><name sortKey="Kloeckner, Julia" sort="Kloeckner, Julia" uniqKey="Kloeckner J" first="Julia" last="Kloeckner">Julia Kloeckner</name><name sortKey="Kloeckner, Julia" sort="Kloeckner, Julia" uniqKey="Kloeckner J" first="Julia" last="Kloeckner">Julia Kloeckner</name><name sortKey="Wagner, Ernst" sort="Wagner, Ernst" uniqKey="Wagner E" first="Ernst" last="Wagner">Ernst Wagner</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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