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Anionic polymers for decreased toxicity and enhanced in vivo delivery of siRNA complexed with cationic liposomes

Author:
Schlegel, Anne, Largeau, Céline, Bigey, Pascal, Bessodes, Michel, Lebozec, Kristell, Scherman, Daniel, Escriou, Virginie
Source:
Journal of controlled release 2011 v.152 no.3 pp. 393-401
ISSN:
0168-3659
Subject:
biodegradability, cell culture, disease models, gene silencing, liver, mice, plasmids, polymers, small interfering RNA, toxicity
Abstract:
We recently reported a cationic lipid-based vector of siRNA, termed siRNA lipoplex that was very efficient in specific gene silencing, both in cell culture and in mouse disease models. To be more efficient, this vector included the addition of a plasmid DNA as an anionic “cargo.” Although this plasmid DNA was devoid of any eukaryotic expression cassette, we decided to replace it by an anionic polymer that would be more acceptable for clinical applications. We identified seven anionic polymers, regarded as non-toxic, biodegradable, of various characteristics and nature. The addition of polymers to siRNA lipoplexes led to the formation of particles with similar characteristics to crude siRNA lipoplexes, decreased cellular toxicity and variable in vitro gene silencing efficiency depending on the type of polymer used. Upon i.v. injection in mice, siRNA lipoplexes prepared with the best polymer, polyglutamate, led to significantly increased recovery of siRNA in liver and lung compared with lipoplexes without polymer.
Agid:
1009911