Use of a bacterial component to enhance targeted delivery of...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/87 (2006.01) A61K 47/48 (2006.01)

Patent

CA 2192687

An improved soluble molecular complex for targeting a polynucleotide to a specific cell is disclosed. The molecular complex comprises: (a) a polynucleotide; (b) a carrier made up of a polynucleotide binding agent and a cell-specific binding agent which binds to a surface molecule of the cell and is internalized into an endosome, and (c) a bacterial component or fragment thereof which lyses the endosome and causes the polynucleotide to be released into the cytoplasm of the cell. In a preferred embodiment of the invention the polynucleotide binding agent is polylysine, the cell-specific binding agent is an asialoglycoprotein, and the bacterial component is listeriolysin O. The disclosed soluble molecular complex and methods of use can be used therapeutically to deliver genes and antisense polynucleotides to specific cells in vivo.

L'invention concerne un complexe moléculaire soluble amélioré permettant un apport ciblé d'un polynucléotide à une cellule spécifique. Le complexe moléculaire comprend (a) un polynucléotide, (b) un véhicule constitué d'un agent de liaison du polynucléotide ainsi qu'un agent de liaison spécifique à la cellule qui se lie à une molécule de surface de la cellule et qui se transforme intérieurement en endosome, et (c) un composant bactérien ou un fragment de celui-ci qui effectue la lyse de l'endosome et provoque la libération du polynucléotide dans le cytoplasme de la cellule. Dans un mode préférentiel de réalisation de l'invention, l'agent de liaison du polynucléotide est la polylysine, l'agent de liaison spécifique à la cellule est une asialoglycoprotéine, et le composant bactérien est la listériolysine O. Le complexe moléculaire soluble décrit dans l'invention ainsi que les procédés d'utilisation de l'invention peuvent être utilisés en thérapie pour administrer des gènes et des polynucléotides antisense à des cellules spécifiques in vivo.

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