Linked Life Data

11087563

Source:http://linkedlifedata.com/resource/pubmed/id/11087563

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2000-12-4
pubmed:abstractText
We have designed and synthesized original cationic lipids for modulated release of DNA from cationic lipid/DNA complexes. Our rationale was that modulated degradation of the lipids during or after penetration into the cell could improve the trafficking of DNA to the nucleus resulting in increased transgene expression. The new reduction-sensitive lipopolyamines (RSL) harbor a disulfide bridge within different positions in the backbone of the lipids as biosensitive function. A useful synthetic method was developed to obtain, with very good yields and reproducibility, unsymmetrical disulfide-bridged molecules, starting from symmetrical disulfides and thiols. The new lipopolyamines are good candidates as carriers of therapeutic genes for in vivo gene delivery. To optimize the transfection efficiency in these novel series, we have carried out structure-activity relationship studies by placing the disulfide bridge at different positions in the backbone of the cationic lipid and by systematic variation of lipid chain length. Results indicate that the transfection level can be modulated as a function of the location of the disulfide bridge in the molecule. We suggest that an early release of DNA during or after penetration into the cell, probably promoted by reduction of a disulfide bridge placed between the polyamine and the lipid, implies a total loss of transfection efficiency. On the other hand, proper modulation of DNA release by inserting the disulfide bridge between one lipid chain and the rest of the molecule brings about increased transfection efficiency as compared to previously described nondegradable lipopolyamine analogues. Finally, preliminary physicochemical characterization of the complexes demonstrates that DNA release from complexes can be modulated as a function of the surrounding reducing conditions of the complexes and of the localization of the disulfide bridge within the lipopolyamine. Our results suggest that RSL is a promising new approach for gene delivery.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4377-87
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11087563-Animals, pubmed-meshheading:11087563-Blood Proteins, pubmed-meshheading:11087563-Cattle, pubmed-meshheading:11087563-Cell Line, pubmed-meshheading:11087563-DNA, pubmed-meshheading:11087563-Disulfides, pubmed-meshheading:11087563-Fluorescence, pubmed-meshheading:11087563-Gene Expression, pubmed-meshheading:11087563-Gene Transfer Techniques, pubmed-meshheading:11087563-Humans, pubmed-meshheading:11087563-Light, pubmed-meshheading:11087563-Lipids, pubmed-meshheading:11087563-Luciferases, pubmed-meshheading:11087563-Oxidation-Reduction, pubmed-meshheading:11087563-Particle Size, pubmed-meshheading:11087563-Polyamines, pubmed-meshheading:11087563-Scattering, Radiation, pubmed-meshheading:11087563-Structure-Activity Relationship, pubmed-meshheading:11087563-Transfection, pubmed-meshheading:11087563-Transgenes
pubmed:year
2000
pubmed:articleTitle
Reduction-sensitive lipopolyamines as a novel nonviral gene delivery system for modulated release of DNA with improved transgene expression.
pubmed:affiliation
Laboratory of Peptidomimetics and Genetic Chemistry, Department of Chemistry, Bar Ilan University, 52900-Ramat Gan, Israel. bykger@mail.biu.ac.il
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't