Repressor on IFN-λ promoter and siRNA against ZEB1 and BLIMP-1 to increase IFN-λ gene activity

摘要

The present invention is directed to the identification of a novel repressor located between ˜1.2 kb to ˜1.6 kb from the translation start site of the IFN-λ1 promoter. The present invention provides a method of using siRNAs against ZEB1 (binds to the repressor region) and BLIMP-1 (binds outside the repressor region) and increases the promoter activity of IFN-λ1 (i.e., increases the production of IFN-λ1 protein). siRNAs against ZEB1 mRNA or BLIMP-1 mRNA increase IFN-λ1 gene activity. There is provided a therapeutic application of siRNAs against ZEB1 and BLIMP-1 mRNAs in treating a mammal (including a human) by increasing the production of IFN-λ1 protein that promotes an anti-viral response as well as treats asthma diseases.

主权项

1. A method of increasing IFN-λ1 gene activity in a mammalian cell, comprising the steps of:
(a) providing a mammalian cell in need of increasing IFN-λ1 gene activity, said mammalian cell is viral-stimulated; and (b) exposing said mammalian cell to a siRNA oligonucleotide targeted against BLIMP1 transcriptional factor mRNA, thereby increasing IFN-λ1 gene activity in said mammalian cell, as indicated by either an increase in IFN-λ1 mRNA or IFN-λ1 protein.