RNA INTERFERENCE MEDIATED INHIBITION OF PROLYL HYDROXYLASE DOMAIN 2 (PHD2) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (SINA)
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 (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against PHD2 gene expression.
1 . A double-stranded short interfering nucleic acid (siNA) molecule comprising R-008039846-001E, R-008039847-001N, R-008039882-001P, R-008039848-001X, R-008039849-001F, R-008053961-001S, R-008054086-001B, R-008147454-000S or any combination thereof.
2 . A composition comprising R-008039846-001E, R-008039847-001N, R-008039882-001P, R-008039848-001X, R-008039849-001F, R-008053961-001S, R-008054086-001B, R-008147454-000S or any combination thereof and a pharmaceutically acceptable carrier or diluent.
3 . A composition comprising:
(a) R-008039846-001E, R-008039847-001N, R-008039882-001P, R-008039848-001X, R-008039849-001F, R-008053961-001S, R-008054086-001B, R-008147454-000S or any combination thereof;
(b) a cationic lipid;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
4 . A composition comprising:
(a) R-008039846-001E, R-008039847-001N, R-008039882-001P, R-008039848-001X, R-008039849-001F, R-008053961-001S, R-008054086-001B, R-008147454-000S or any combination thereof;
(b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
5 . The composition according to claim 4 , wherein the (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, cholesterol, DSPC, and PEG-DMG have a molar ratio of 50:30:10:2 respectively.
6 . A composition comprising the composition according to claim 5 and a pharmaceutically acceptable carrier or diluent.
7 . A method of treating a human subject suffering from a condition which is mediated by the action, or by loss of action, of PHD2, which comprises administering to said subject an effective amount of R-008039846-001E, R-008039847-001N, R-008039882-001P, 8-008039848-001X, R-008039849-001F, R-008053961-001S, R-008054086-001B, R-008147454-000S or any combination thereof.
8 . The method according to claim 7 , wherein the condition is anemia.
9 . The method according to claim 7 , further comprising administration of a chemotherapeutic agent.
10 . A kit comprising R-008039846-001E, R-008039847-001N, R-008039882-001P, 8-008039848-001X, R-008039849-001F, R-008053961-001S, R-008054086-001B, R-008147454-000S or any combination thereof.
11 . A composition comprising R-008039846-001E and R-008147454-000S.
12 . A composition comprising R-008039846-001E and R-008147454-000S and a pharmaceutically acceptable carrier or diluent.
13 . A composition comprising:
(a) R-008039846-001E and R-008147454-000S;
(b) a cationic lipid;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
14 . A composition comprising:
(a) R-008039846-001E and R-008147454-000S;
(b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
15 . The composition according to claim 14 , wherein the (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, cholesterol, DSPC, and PEG-DMG have a molar ratio of 50:30:10:2 respectively.
16 . A composition comprising the composition according to claim 15 and a pharmaceutically acceptable carrier or diluent.
17 . A method of treating a human subject suffering from a condition which is mediated by the action, or by loss of action, of PHD2, which comprises administering to said subject an effective amount of R-008039846-001E and R-008147454-000S.
18 . The method according to claim 17 , wherein the condition is anemia.
19 . The method according to claim 17 , further comprising administration of a chemotherapeutic agent.
20 . A kit comprising the double-stranded short interfering nucleic acid (siNA) according to claim 11 .