Preparation of stable formulations of lipid-nucleic acid...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/88 (2006.01) A61K 9/127 (2006.01) A61K 9/66 (2006.01) A61K 47/48 (2006.01) A61K 48/00 (2006.01) C07H 21/00 (2006.01) C07H 21/02 (2006.01) C07H 21/04 (2006.01)

Patent

CA 2271325

The present invention provides for lipid:nucleic acid complexes that have increased shelf life and high transfection activity in vivo following intravenous injection, and methods of preparing such complexes. The methods generally involve contacting a nucleic acid with an organic polycation to produce a condensed nucleic acid, and then combining the condensed nucleic acid with a lipid comprising an amphiphilic cationic lipid to produce the lipid:nucleic acid complex. This complex can be further stabilized by the addition of a hydrophilic polymer attached to hydrophobic side chains. The complex can also be made specific for specific cells, by incorporating a targeting moiety such as a Fab' fragment attached to a hydrophilic polymer.

La présente invention a trait à des complexes de type lipide-acide nucléique présentant une durée de conservation accrue, et une activité élevée de transfection in vivo suite à une injection intraveineuse, et à des procédés de préparation de tels complexes. Ces procédés comprennent généralement les étapes consistant à mettre en contact un acide nucléique avec un polycation organique pour produire un acide nucléique condensé, puis à combiner l'acide nucléique condensé avec un lipide contenant un lipide cationique amphiphile, en vue de produire le complexe lipide-acide nucléique. Ce complexe peut ensuite être stabilisé par addition d'un polymère hydrophile fixé à des chaînes latérales hydrophobes. Ce complexe peut également être rendu spécifique pour des cellules spécifiques, par incorporation d'une fraction de ciblage, tel un fragment Fab' fixé à un polymère hydrophile.

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