Dsrna for treating viral infection

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/11 (2006.01) A61K 31/713 (2006.01) C07H 21/00 (2006.01)

Patent

CA 2692503

The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (P14K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes.

L'invention concerne des acides ribonucléiques double brin (ARNdb) ciblant l'expression génique de la phosphatidylinositol 4-kinase (PI4K), en particulier, du polypeptide bêta, catalytique (PIK4CB) de la phosphatidylinositol 4-kinase humaine ou du polypeptide alpha, catalytique (PIK4CA) de la la phosphatidylinositol 4-kinase humaine, et leur utilisation pour traiter l'infection par un virus de type ARN à brin positif tel que le virus de l'hépatite C (VHC). Chaque ARNdb comprend un brin antisens ayant une séquence de nucléotides d'une longueur inférieure à 30 nucléotides, généralement, d'une longueur de 19-25 nucléotides, et qui est sensiblement complémentaire d'au moins une partie de l'ARNm PIK4CB ou PIK4CA cible. Une pluralité de ces ARNdb peut être utilisée pour obtenir un avantage thérapeutique. L'invention concerne également une composition pharmaceutique comprenant l'ARNdb avec un véhicule pharmaceutiquement acceptable, et comprenant une modalité de délivrance telle que des liposomes entièrement encapsulés ou des complexes lipidiques. L'invention comprend, en outre, des procédés pour traiter les maladies provoquées par une infection par un virus de type ARN à brin positif en utilisant les compositions pharmaceutiques; et des procédés pour inhiber la propagation intra- et intercellulaire des virus de type ARN à brin positif.

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