Document Detail


Polyplexes and lipoplexes for mammalian gene delivery: from traditional to microarray screening.
MedLine Citation:
PMID:  15320709     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gene therapy requires the development of non-toxic and highly efficient delivery systems for DNA and RNAi. Polycations, especially dendrimers, have shown enormous potential as gene transfer vehicles, displaying minimal toxicity with a broad range of cell lines. In this paper, a total of 13 dendrimers, up to G3.0, were constructed from AB(3) type isocyanate monomers using solid phase methodology and evaluated for transfection activity. Among the library of compounds prepared, a G3.0 dendrimer displayed comparable activity to Superfect. Gel retardation assays demonstrated that all of the compounds completely bound plasmid DNA, indicating the efficient formation of complexes between DNA and the dendrimers. A "transfection microarray" approach was developed for screening these compounds as well as a panel of lipoplexes (complexes of DNA with cationic lipids) and polyplexes (complexes of DNA with synthetic polycationic polymers), in 3D solution like micro-assay). Five cationic lipids with a cholesterol tail showed stronger or comparable transfection activity relative to Effectene. The new, micro-array screening method was rapid and miniaturized, offering the potential of high throughput screening of large libraries of transfection candidates, with thousands of library members per array, and the ability to rapidly screen a broad range of cell types.
Authors:
S E How; B Yingyongnarongkul; M A Fara; J J Díaz-Mochón; S Mittoo; M Bradley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Combinatorial chemistry & high throughput screening     Volume:  7     ISSN:  1386-2073     ISO Abbreviation:  Comb. Chem. High Throughput Screen.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-23     Completed Date:  2004-10-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9810948     Medline TA:  Comb Chem High Throughput Screen     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  423-30     Citation Subset:  IM    
Affiliation:
Department of Chemistry, University of Southampton, Southampton, Hampshire SO171BJ, UK.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
DNA / administration & dosage*
Drug Delivery Systems
Drug Evaluation, Preclinical
Electrophoresis, Agar Gel
Gene Transfer Techniques*
Humans
Lipids / chemistry
Oligonucleotide Array Sequence Analysis / methods*
Polymers / chemistry
Tetrazolium Salts
Thiazoles
Transfection
Vehicles
Chemical
Reg. No./Substance:
0/Lipids; 0/Polymers; 0/Tetrazolium Salts; 0/Thiazoles; 0/Vehicles; 298-93-1/thiazolyl blue; 9007-49-2/DNA

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