RNA interference mediated inhibition of prolyl hydroxylase domain 2 (PHD2) gene expression using short interfering nucleic acid (siNA)

摘要

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of PHD2 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsR-NA), micro-RNA (miRNA), and short hair-pin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against PHD2 gene expression.

主权项

1. An isolated double-stranded short interfering nucleic acid (siNA) molecule that inhibits expression of prolyl hydroxylase domain 2 (PHD2), comprising5′-B cAuuGAAcccAAAuuuGAuTT B-3′(SEQ ID NO: 347)and5′-AUCAAAuuuGGGuucAAuGUU-3′;(SEQ ID NO: 348)5′-BGcAAuAAcuGuuuGGuAuuTTB-3′(SEQ ID NO: 312)and5′-AAUAccAAAcAGuuAuuGcUU-3′;(SEQ ID NO: 313)5′-BGuGAcAuGuAuAuAuuAucTTB-3′(SEQ ID NO: 470)and5′-GAUAAuAuAuAcAuGucAcUU-3′;(SEQ ID NO: 471)5′-BAuGcuAcAAGGuAcGcAAuTTB-3′(SEQ ID NO: 405)and5′-AUUGcGuAccuuGuAGcAuUU-3′;(SEQ ID NO: 406)5′-BAAGGuAcGcAAuAAcuGuuTTB-3′(SEQ ID NO: 500)and5′-AACAGuuAuuGcGuAccuuUU-3′;(SEQ ID NO: 501)5′-BcuuGuuuGuGGuAcuucAuTTB-3′(SEQ ID NO: 1055)and5′-AUGAAGuAccAcAAAcAAGUU-3′;(SEQ ID NO: 1056)5′-BGAAAGGuGuucAAGuAccATTB-3′(SEQ ID NO: 1057)and5′-UGGuAcuuGAAcAccuuucUU-3′;(SEQ ID NO: 1058)or5′-B ccuGuAucuAcuAccuGAATT B-3′(SEQ ID NO: 1059)and5′-UUCAGGuAGuAGAuAcAGGUU-3′;(SEQ ID NO: 1060) wherein A, C, G, and U are ribose A, C, G or U; a, g, c and u are 2′-deoxy-2′-fluoro A, G, C or U; A, U, C and G are 2′-O-methyl (2′-OMe) A, U, C, or G; A, U, C, and G are deoxy A, U, C, or G; B is inverted abasic; and T is thymidine.