Linked Life Data

8844203

Source:http://linkedlifedata.com/resource/pubmed/id/8844203

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-1-16
pubmed:abstractText
We have examined the complement-activating properties of synthetic cationic molecules and their complexes with DNA. Commonly used gene delivery vehicles include complexes of DNA with polylysine of various chain lengths, transferrin-polylysine, a fifth-generation poly(amidoamine) (PAMAM) dendrimer, poly(ethyleneimine), and several cationic lipids (DOTAP, DC-Chol/DOPE, DOGS/DOPE, and DOTMA/DOPE). These agents activate the complement system to varying extents. Strong complement activation is seen with long-chain polylysines, the dendrimer, poly(ethyleneimine), and DOGS (half-maximal at about 3 microM amine content in the assay used). Compared to these compounds, the other cationic lipids (in liposome formulations) are weak activators of the complement system (half-maximal approximately 50-100 microM positive charge in assay). Complement activation by polylysine is strongly dependent on the chain length. Short-chain oligolysines are comparable to cationic lipids in their activation of complement. Incubation of these compounds with DNA to form complexes reduces complement activation in virtually all cases. The degree of complement activation by DNA complexes is strongly dependent on the ratio of polycation and DNA (expressed as the charge ratio) for polylysine, dendrimer, poly(ethyleneimine), and DOGS. To a lesser degree, charge ratio also influences complement activation by monovalent cationic lipid-DNA complexes. For polylysine-DNA complexes, complement activation can be considerably reduced by modifying the surface of preformed DNA complexes with polyethyleneglycol (half-maximal approximately 20 microM amine content). The data suggests that, by appropriate formulation of DNA complexes, complement activation can be minimized or even avoided. These findings should facilitate the search for DNA complex formulations appropriate for reproducible intravenous gene delivery.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1,2-dielaidoylphosphatidylethanolami..., http://linkedlifedata.com/resource/pubmed/chemical/1,2-dioleoyloxy-3-(trimethylammonium..., http://linkedlifedata.com/resource/pubmed/chemical/Cations, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Recombinant, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Monounsaturated, http://linkedlifedata.com/resource/pubmed/chemical/Glycine, http://linkedlifedata.com/resource/pubmed/chemical/Liposomes, http://linkedlifedata.com/resource/pubmed/chemical/N-(1-(2,3-dioleyloxy)propyl)-N,N,N-t..., http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylethanolamines, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids, http://linkedlifedata.com/resource/pubmed/chemical/Polylysine, http://linkedlifedata.com/resource/pubmed/chemical/Quaternary Ammonium Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Spermine, http://linkedlifedata.com/resource/pubmed/chemical/dioctadecylamidoglycylspermine
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1437-46
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery.
pubmed:affiliation
University of California, School of Pharmacy, San Francisco 94143-0446, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't