| Comparison between the interactions of adenovirus-derived peptides with plasmid DNA and their role in gene delivery mediated by liposome-peptide-DNA virus-like nanoparticles. | |
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MedLine Citation:
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PMID: 12956058 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previously we have described the development and applications of an important new platform system for gene delivery known as liposome-mu-DNA (LMD), prepared from cationic liposomes (L), plasmid DNA (D) and the mu(M) peptide derived from the adenovirus core. In an attempt to improve upon mu, an alternative peptide (pepV) derived from the adenovirus peptide/protein-DNA core complex was identified, synthesised and studied alongside mu using a number of biophysical techniques including gel retardation, ethidium bromide exclusion, CD binding titration, DNA melting, and plasmid protection assays. PepV binds to pDNA less efficiently than mu but is able to charge neutralise and condense pDNA into negatively charged pepVD particles comparable in dimension to MD particles. The results of CD studies and plasmid protection assays suggest that peptide-DNA interactions are likely to cause pDNA condensation by a combination of charge neutralisation, base pair tilting, double helix destabilisation and the induction of pDNA superfolding. Data suggest the pepVD particles may be formulated with cationic liposomes to give defined LpepVD particles that appear to transfect HeLa cells with marginally more efficiency than LMD particles suggesting that pepV may have some effect on the pDNA transcription process. Although pepV harbours a nuclear-nucleolar localisation sequence (NLS), transfection data show that this capacity is not being appropriately harnessed by the current LpepVD formulation. Further improvements may be required in terms of optimising LpepVD formulations--for instance, to ensure the integrity of the peptide-DNA complexes following cell entry--in order to fully exploit the full NLS capacity of the peptide, thereby facilitating the transfection of slowly dividing or quiescent cells. |
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Authors:
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Monika Preuss; Miriam Tecle; Imran Shah; David A Matthews; Andrew D Miller |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Organic & biomolecular chemistry Volume: 1 ISSN: 1477-0520 ISO Abbreviation: Org. Biomol. Chem. Publication Date: 2003 Jul |
Date Detail:
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Created Date: 2003-09-05 Completed Date: 2003-12-09 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 101154995 Medline TA: Org Biomol Chem Country: England |
Other Details:
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Languages: eng Pagination: 2430-8 Citation Subset: IM |
Affiliation:
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Imperial College Genetic Therapies Centre, Department of Chemistry, Flowers Building, Armstrong Road, Imperial College London, London, UK SW7 2AZ. m.preuss@imperial.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics,
metabolism* Amino Acid Sequence Calorimetry Cell Survival / drug effects Circular Dichroism DNA / administration & dosage, chemistry, genetics* Gene Transfer Techniques* Hela Cells Humans Liposomes / administration & dosage, chemistry* Molecular Sequence Data Nanotechnology Nucleic Acid Conformation Peptides / chemistry*, metabolism*, pharmacology Plasmids / chemistry, genetics*, metabolism Spectrometry, Fluorescence Spectrophotometry / methods Thermodynamics Transfection Viral Core Proteins / chemistry, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Liposomes; 0/Peptides; 0/Viral Core Proteins; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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