Oligonucleotides with nucleoside analogs
siRNA compositions are provided that contain gemcitabine (GEM) in place of cytosine moieties within the siRNA sequence. Pharmaceuticals compositions containing these siRNA molecules, and methods of using the compositions for treating diseases such as cancer are provided.
1 . An siRNA comprising a sense strand having the sequence:
(SEQ ID NO: 18)
5′-CCU GUG GAA UAG UAC UUA CUG CAA U-3′
and an antisense strand having the sequence
(SEQ ID NO: 2)
5′-A UUG CAG UAA GUA CUA UUC CAC AGG-3′,
wherein one or more cytosine moieties within the sense strand are replaced by a gemcitabine moiety.
2 . The siRNA of claim 1 , wherein said sense strand has the sequence:
(SEQ ID NO: 18)
SS = 5′-CCU GUG GAA UAG UAC* UUA C*UG C*AA U-3′,
wherein C* represents a cytosine moiety replaced by a gemcitabine moiety.
3 . An siRNA sequence against mouse and human genes for RAD17, wherein the sense strand (SS) is
RAD17_7(6):
(SEQ ID NO: 23)
SS-5′CCAACAAUUAUGAUGAAAUUUCUUA-3′
and wherein one or more cytosine moieties within the sense strand are replaced by a gemcitabine moiety.
4 . The siRNA of claim 3 , wherein sense strand of the siRNA comprises the sequence:
(SEQ ID NO: 32)
SS-5′CCAAC*AAUUAUGAUGAAAUUUC*UUA-3′
wherein C* represents a cytosine moiety replaced by a gemcitabine moiety.
5 . A composition comprising the siRNA of claim 1 and a pharmaceutically acceptable carrier.
6 . The composition of claim 5 , wherein the pharmaceutically acceptable carrier comprises a branched histidine-lysine co-polymer.
7 . A composition comprising the siRNA of claim 3 and a pharmaceutically acceptable carrier.
8 . The composition of claim 7 , wherein the pharmaceutically acceptable carrier comprises a branched histidine-lysine co-polymer.
9 . The siRNA of claim 1 , wherein the siRNA is chemically modified and attached directly to a targeting ligand that comprises GalNac.
10 . The siRNA of claim 3 , wherein the siRNA is chemically modified and attached directly to a targeting ligand that comprises GalNac.