Multiple rna polymerase iii promoter expression constructs

C - Chemistry – Metallurgy – 12 – N

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C12N 15/85 (2006.01) A61K 48/00 (2006.01) A61P 31/12 (2006.01) C12N 15/11 (2006.01)

Patent

CA 2577519

Expression constructs comprising at least two different RNA polymerase III promoters, wherein each promoter is operably linked to a nucleic acid sequence encoding an RNA effector molecule, are disclosed herein. Further provided are expression constructs comprising multiple polymerase III promoters operably linked to sequences encoding short hairpin RNA molecules, which may comprise single and/or multiple fingers. The provided constructs are useful for in vivo delivery of RNA molecules effective in gene silencing, including of viral genes including HBV and HCV.

L'invention concerne une construction d'expression comprenant au moins deux promoteurs de d'ARN polymérase III différents, chaque promoteur étant relié fonctionnel à une séquence d'acides nucléiques codant une molécule effectrice d'ARN. L'invention concerne également des constructions d'expression comprenant des promoteurs de polymérase III multiples reliés fonctionnel à des séquences codant des molécules d'ARN courtes en épingle à cheveux, à doigt unique et/ou multiples. Les constructions de l'invention sont utilisés dans l'administration in vivo de molécules ARN efficaces dans le silençage génique, notamment celui des gènes viraux tels que le VHB et le VHC

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