Cellular signal-responsive gene transcriptional regulation...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/87 (2006.01) A61K 48/00 (2006.01) C07K 14/47 (2006.01)

Patent

CA 2447538

A gene complex-forming material which comprises a water-soluble polymer having a peptide containing an amino acid sequence serving as the substrate of an intracellular signal-responsive enzyme and basic amino acids imparting cationic nature; a gene complex composed of this gene complex-forming material with a gene; and a gene transfer method and a gene transfer agent with the use of the same. Namely, a novel material and a method wherein the cationic moiety of the peptide and the gene form a rigid ion complex to give a stable gene complex, and, upon a cellular signal response, the positive charge of the cationic moiety of the peptide is neutralized or disappears and the gene complex is broken in the cell to thereby release the gene, thus activating the gene transferred into specific cells. The neutralization or disappearance of the positive charge can be achieved by, for example, phosphorylation with protein kinase A or cleavage by caspase.

L'invention concerne une matière de formation d'un complexe génique, comprenant un polymère soluble dans l'eau avec un peptide contenant une séquence d'acides aminés servant de substrat à une enzyme répondant à un signal intracellulaire et des acides aminés de base de nature cationique ; un complexe génique composé de ladite matière de formation de complexe génique avec un gène ; et une méthode de transfert de gène et un agent de transfert de gène utilisant ladite méthode. L'invention concerne plus précisément une nouvelle matière et une méthode dans laquelle le fragment cationique du peptide et le gène forment un complexe ionique rigide permettant d'obtenir un complexe génique stable et, suite à la réponse à un signal cellulaire, la charge positive du fragment cationique du peptide est neutralisée ou disparaît et le complexe génique est rompu dans la cellule de manière à libérer le gène, activant ainsi le gène transféré dans des cellules spécifiques. La neutralisation ou disparition de la charge positive peut être obtenue, par exemple, par phosphorylation à l'aide de la protéine kinase A ou par clivage par caspase.

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