C/EBP ALPHA SARNA COMPOSITIONS AND METHODS OF USE
The invention relates to saRNA targeting a C/EBPα transcript and therapeutic compositions comprising said saRNA. Methods of using the therapeutic compositions are also provided.
1 . A method of increasing white blood cell (WBC) or neutrophils (NEU) levels comprising administering a synthetic isolated saRNA which up-regulates the expression of C/EBPα gene, wherein the saRNA comprises a strand with a sequence that is at least 80% complementary to a region on SEQ ID No. 3, and wherein the strand has 14-30 nucleotides.
2 . The method of claim 1 , wherein the saRNA comprises a strand with SEQ ID No. 1.
3 . The method of claim 1 , wherein the saRNA is double-stranded and comprises an antisense strand of SEQ ID No. 1 and a sense strand of SEQ ID No. 2.
4 . The method of claim 1 , wherein the saRNA is encapsulated into liposomes.
5 . The method of claim 4 , wherein the liposome comprises 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), cholesteryl-hemi succinate (CHEMS), and 4-(2-aminoethyl)-morpholino-cholesterol hemisuccinate (MOCHOL).
6 . The method of claim 5 , wherein the molar ratio of POPC:DOPE:CHEMS:MOCHOL is around 6:24:23:47.
7 . The method of claim 4 , wherein the size of the liposome is between about 50 nm to about 150 nm or between about 100 nm to about 120 nm.
8 . The method of claim 1 , wherein WBC count or neutrophil count increases at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130%, 140%, 150%, two folds, three folds, four folds, five folds, or ten folds compared to the WBC count or neutrophil count before saRNA administration.
9 . A method of reducing inflammation of a cell comprising administering a synthetic isolated saRNA which up-regulates the expression of C/EBPα gene, wherein the saRNA comprises a strand with a sequence that is at least 80% complementary to a region on SEQ ID No. 3, and wherein the strand has 14-30 nucleotides.
10 . The method of claim 9 , wherein the saRNA comprises a strand with SEQ ID No. 1.
11 . The method of claim 9 , wherein the saRNA is double-stranded and comprises an antisense strand of SEQ ID No. 1 and a sense strand of SEQ ID No. 2.
12 . The method of claim 9 , wherein the saRNA is encapsulated into liposomes.
13 . The method of claim 12 , wherein the liposome comprises 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), cholesteryl-hemisuccinate (CHEMS), and 4-(2-aminoethyl)-morpholino-cholesterol hemisuccinate (MOCHOL).
14 . The method of claim 13 , wherein the molar ratio of POPC:DOPE:CHEMS:MOCHOL is around 6:24:23:47.
15 . The method of claim 12 , wherein the size of the liposome is between about 50 nm to about 150 nm or between about 100 nm to about 120 nm.
16 . The method of claim 1 , wherein the cell is a white blood cell.
17 . The method of claim 16 , wherein the interferon gamma (IFN-gamma), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), and/or interleukin 6 receptor (IL6-R) levels are reduced.
18 . The method of claim 17 , wherein the level of IFN-gamma, NFkB, or IL6-R decrease at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, or 80% compared to the level of IFN-gamma, NFkB, or IL6-R before saRNA administration.
19 . A method of up-regulating CEBPA gene expression in a subject comprising administering a double-stranded saRNA comprises an antisense strand of SEQ ID No. 1 and a sense strand of SEQ ID No. 2, wherein the subject receives at least two doses of the saRNA, wherein the doses are 24 hours or 48 hours apart.
20 . The method of claim 19 , wherein the saRNA is encapsulated into liposomes.
21 . The method of claim 20 , wherein the liposome comprises 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), cholesteryl-hemi succinate (CHEMS), and 4-(2-aminoethyl)-morpholino-cholesterol hemisuccinate (MOCHOL).
22 . The method of claim 21 , wherein the molar ratio of POPC:DOPE:CHEMS:MOCHOL is around 6:24:23:47.
23 . The method of claim 19 , wherein the CEBPA gene expression in the liver of the subject is increased.
24 . The method of claim 19 , wherein the subject has a liver disease.
25 . The method of claim 24 , wherein the subject has liver fibrosis.
26 . The method of claim 19 , wherein the subject receives 2 doses 48 hours apart.
27 . The method of claim 19 , wherein the subject receives 3 doses 24 hours apart.