Capped synthetic rna, analogs, and aptamers

C - Chemistry – Metallurgy – 07 – H

Patent

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C07H 21/02 (2006.01) A61K 31/70 (2006.01) C07H 21/00 (2006.01) C12N 15/11 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2223549

A method is provided for making synthetic capped RNAs. These compounds serve as substrates for the virally encoded endonuclease associated with influenza virus. We are able to assay for this unique and specific viral activity of cleavage of a capped RNA in vitro. Therefore, screening of inhibitors of this activity is possible. In addition, short non-extendible (due to their length or because of the modification of the 3'-end of the oligo, i.e. 3'-dA) RNAs are potent inhibitors of the cleavage of capped RNAs by influenza endonuclease. Finally, these compounds may be used to investigate viral and cellular mechanisms of transcription/translation or mRNA maturation.

L'invention porte sur un procédé permettant de produire des ARN synthétiques à coiffe. Ces composés font office de substrats pour les endonucléases à codage viral qui sont associés au virus de la grippe. L'invention permet de doser l'activité virale unique et spécifique du clivage in vitro d'un ARN à coiffe. Ainsi, le triage des inhibiteurs de cette activité est réalisable. En outre, les ARN courts non extensibles (en raison de leur longueur ou de la modification de l'extrémité 3' de l'oligo, c.-à-d. 3'-dA) sont de puissants inhibiteurs du clivage des ARN à coiffe par les endonucléases de la grippe. En dernier lieu, on peut utiliser ces composés pour rechercher les mécanismes viraux et cellulaires de transcription/traduction ou de maturation de l'ARN messager.

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