COMPOSITIONS AND METHODS OF USING C/EBP ALPHA SARNA
The disclosure relates to a pharmaceutical composition comprising an saRNA targeting C/EBPα and at least one additional active agent. Methods of using the pharmaceutical composition are also provided.
1 . A method of blocking MDSC's or TAM's inhibitory activity against T-cell proliferation in a subject in need thereof, comprising administering a synthetic isolated saRNA to the subject, wherein the saRNA comprises an antisense strand with a sequence of SEQ ID No. 1 (CEBPA-51).
2 . The method of claim 1 , wherein the saRNA is double-stranded and further comprises a sense strand.
3 . The method of claim 2 , wherein the sense strand of the saRNA comprises a sequence of SEQ ID No. 2 (CEBPA-51).
4 . The method of claim 3 , wherein CEBPA-51 is delivered with liposomes.
5 . The method of claim 4 , wherein the liposomes are NOV340 Smarticles.
6 . The method of claim 1 , wherein the T-cell proliferation is up-regulated by at least 20%, 50%, 100%, 2 folds, 3 folds, 4 folds or 5 folds.
7 . The method of claim 1 , where in the subject has tumor.
8 . The method of claim 1 , wherein the subject has lung cancer or colon cancer.
9 . A method of up-regulating the expression of the C/EBPα gene in a cell in a subject in need thereof, wherein the cell is a monocytic myeloid-derived suppressor cell (MDSC) or a tumor associated macrophage (TAM), comprising administering a synthetic isolated saRNA to the cell, wherein the saRNA comprises an antisense strand with a sequence of SEQ ID No. 1 (CEBPA-51).
10 . The method of claim 9 , wherein the saRNA is double-stranded and further comprises a sense strand.
11 . The method of claim 10 , wherein the sense strand of the saRNA comprises a sequence of SEQ ID No. 2 (CEBPA-51).
12 . The method of claim 11 , wherein CEBPA-51 is delivered with liposomes.
13 . The method of claim 12 , wherein the liposomes are NOV340 Smarticles.
14 . The method of claim 9 , wherein the expression of the C/EBPα gene is up-regulated by at least 20%, 50%, 100%, 2 folds, 3 folds, 4 folds or 5 folds.
15 . The method of claim 9 , where in the subject has tumor.
16 . The method of claim 9 , wherein the subject has lung cancer or colon cancer.
17 . A method of reducing the expression of a target gene in a cell in a subject in need thereof, comprising administering a synthetic isolated saRNA to the cell, wherein the saRNA comprises an antisense strand with a sequence of SEQ ID No. 1 (CEBPA-51), wherein the target gene is ARG1, iNOS, S100A8 or S100A9.
18 . The method of claim 17 , wherein the saRNA is double-stranded and further comprises a sense strand.
19 . The method of claim 18 , wherein the sense strand of the saRNA comprises a sequence of SEQ ID No. 2 (CEBPA-51).
20 . The method of claim 19 , wherein CEBPA-51 is delivered with liposomes.
21 . The method of claim 20 , wherein the liposomes are NOV340 Smarticles.
22 . The method of claim 17 , wherein the target gene expression is reduced by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, or 80%.
23 . The method of claim 17 , wherein the cell is MDSC or TAM.
24 . The method of claim 17 , where in the subject has tumor.
25 . The method of claim 18 , wherein the subject has lung cancer or colon cancer.
26 . A method of delivering a synthetic isolated saRNA to myeloid cells of a subject in need thereof, wherein the saRNA comprises an antisense strand with a sequence of SEQ ID No. 1 (CEBPA-51), comprising formulating the saRNA with liposomes.
27 . The method of claim 26 , wherein the saRNA is double-stranded and further comprises a sense strand.
28 . The method of claim 27 , wherein the sense strand of the saRNA comprises a sequence of SEQ ID No. 2 (CEBPA-51).
29 . The method of claim 26 , wherein the liposomes are NOV340 Smarticles.
30 . The method of claim 26 , where in the subject has tumor.
31 . The method of claim 26 , wherein the subject has lung cancer or colon cancer.
32 . A method of treating cancer in a subjection in need thereof, comprising administering a synthetic isolated saRNA to the cell and an additional active agent, wherein the saRNA comprises an antisense strand with a sequence of SEQ ID No. 1 (CEBPA-51), and wherein the additional active agent is a CTLA-4 inhibitor, a COX2 inhibitor, or a FATP2 inhibitor.
33 . The method of claim 32 , wherein the saRNA is double-stranded and further comprises a sense strand.
34 . The method of claim 33 , wherein the sense strand of the saRNA comprises a sequence of SEQ ID No. 2 (CEBPA-51).
35 . The method of claim 32 , wherein CEBPA-51 is delivered with liposomes.
36 . The method of claim 35 , wherein the liposomes are NOV340 Smarticles.
37 . The method of claim 32 , wherein the CTLA-4 inhibitor is a CTLA-4 antibody.
38 . The method of claim 32 , wherein the COX2 inhibitor is celecoxib.
39 . The method of claim 32 , wherein the FATP2 inhibitor is lipofermata.
40 . The method of claim 32 , where the subject has lung cancer or colon cancer.