Document Detail


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.
MedLine Citation:
PMID:  12956058     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Monika Preuss; Miriam Tecle; Imran Shah; David A Matthews; Andrew D Miller
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Organic & biomolecular chemistry     Volume:  1     ISSN:  1477-0520     ISO Abbreviation:  Org. Biomol. Chem.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-09-05     Completed Date:  2003-12-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101154995     Medline TA:  Org Biomol Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  2430-8     Citation Subset:  IM    
Affiliation:
Imperial College Genetic Therapies Centre, Department of Chemistry, Flowers Building, Armstrong Road, Imperial College London, London, UK SW7 2AZ. m.preuss@imperial.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / 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:
0/Liposomes; 0/Peptides; 0/Viral Core Proteins; 9007-49-2/DNA

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