| Balancing protection and release of DNA: tools to address a bottleneck of non-viral gene delivery. | |
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MedLine Citation:
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PMID: 19734186 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Engineering polymeric gene-delivery vectors to release an intact DNA payload at the optimal time and subcellular compartment remains a formidable challenge. An ideal vector would provide total protection of complexed DNA from degradation prior to releasing it efficiently near or within the nucleus of a target cell. While optimization of polymer properties, such as molecular weight and charge density, has proved largely inadequate in addressing this challenge, applying polymeric carriers that respond to temperature, light, pH and redox environment to trigger a switch from a tight, protective complex to a more relaxed interaction favouring release at the appropriate time and place has shown promise. Currently, a paucity of gene carriers able to satisfy the contrary requirements of adequate DNA protection and efficient release contributes to the slow progression of non-viral gene therapy towards clinical translation. This review highlights the promising carrier designs that may achieve an optimal balance of DNA protection and release. It also discusses the imaging techniques and three-dimensional in vitro models that can help study these two barriers in the non-viral gene transfer process. Ultimately, efficacious non-viral gene therapy will depend on the combination of intelligent material design, innovative imaging techniques and sophisticated in vitro model systems to facilitate the rational design of polymeric gene-delivery vectors. |
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Authors:
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Christopher L Grigsby; Kam W Leong |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review Date: 2009-09-04 |
Journal Detail:
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Title: Journal of the Royal Society, Interface / the Royal Society Volume: 7 Suppl 1 ISSN: 1742-5662 ISO Abbreviation: J R Soc Interface Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2009-12-24 Completed Date: 2010-05-03 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 101217269 Medline TA: J R Soc Interface Country: England |
Other Details:
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Languages: eng Pagination: S67-82 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC 27708, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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DNA
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metabolism* Gene Therapy / methods* Gene Transfer Techniques / instrumentation* Genetic Vectors / genetics* Hydrogen-Ion Concentration Magnetic Resonance Imaging / methods Microscopy, Fluorescence / methods Models, Biological* Molecular Structure Polymers / chemistry Spectrometry, Fluorescence / methods |
| Grant Support | |
ID/Acronym/Agency:
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HL89764/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Polymers; 9007-49-2/DNA |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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