Materials and methods for prevention and treatment of rna...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/54 (2006.01) A61K 31/7088 (2006.01) A61K 38/45 (2006.01) A61K 38/51 (2006.01) A61K 48/00 (2006.01) C12N 9/12 (2006.01)

Patent

CA 2484251

The subject invention concerns a method of inhibiting an RNA virus infection within a patient by increasing the amount of 2-5 oligoadenylate (2-5 AS) activity within the patient. Preferably, the preventive and therapeutic methods of the present invention involve administering a nucleotide encoding 2- 5 AS, or at least one catalytically active fragment thereof, such as the p40, p69, p100 subunits to a patient in need thereof. The present inventors have determined that overexpression of 2-5AS causes a reduction in epithelial cell damage, reduction in infiltration of mononuclear cells in the peribronchiolar and perivascular regions, and reduction in thickening of the septa in the lungs. Levels of chemokines, such as MIP1-.alpha., are also reduced upon overexpression of 2-5AS. The subject invention also pertains to pharmaceutical compositions containing a nucleotide sequence encoding 2-5AS and pharmaceutically acceptable carrier, as well as vectors for delivery of the 2- 5AS nucleotide sequence.

L'invention concerne un procédé visant à inhiber une infection par un virus à ARN chez un patient, qui consiste à accroître l'activité de 2-5 oligoadénylate synthétase (2-5 AS) chez ledit patient. De préférence, les méthodes préventives et thérapeutiques de l'invention comprennent l'administration d'un nucléotide codant pour 2-5 AS, ou d'au moins un fragment catalytiquement actif de celui-ci, tel que les sous-unités p40, p69 ou p100, à un patient nécessitant un tel traitement. Les inventeurs ont pu établir que la surexpression de 2-5AS produit une réduction des lésions des cellules épithéliales, une réduction de l'infiltration des cellules mononucléaires dans les régions péribronchiolaires et périvasculaires, et une réduction de l'épaisseur des septa dans les poumons. Les taux de chimiokines telles que MIP1-.alpha., sont également réduits lors de la surexpression de 2-5AS. L'invention se rapporte aussi à des compositions pharmaceutiques qui contiennent une séquence nucléotidique codant pour 2-5AS et un excipient pharmaceutiquement acceptable, et à des vecteurs pour l'apport de la séquence nucléotidique codant pour 2-5AS.

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