STAT3 targeting oligonucleotides and uses thereof
The subject matter disclosed herein is directed to modulating STAT3 gene expression using siRNA compositions and methods directed to affecting key cell populations supporting the growth and metastasis of cancer to affect the beneficial treatment, remission or removal of the underlying tumor in a patient.
1 . An oligonucleotide for reducing STAT3 expression, the oligonucleotide comprising an antisense strand of 15 to 30 nucleotides in length and a sense strand comprising the sequence set forth in SEQ ID NO: 1222, wherein the sense strand and antisense strand form a duplex region and the antisense strand has a region of complementarity to a target sequence of STAT3 as set forth in SEQ ID NO: 140.
2 . The oligonucleotide of claim 1 , wherein the antisense strand comprises a sequence as set forth in SEQ ID NO: 965.
3 . The oligonucleotide of claim 1 , wherein the antisense strand comprises the sequence set forth in SEQ ID NO: 1145.
4 . The oligonucleotide of claim 1 , wherein the oligonucleotide reduces expression of STAT3 mRNA in one or more immune cells associated with a tumor microenvironment.
5 . A pharmaceutical composition comprising the oligonucleotide of claim 1 , and a pharmaceutically acceptable carrier, delivery agent, or excipient.
6 . An oligonucleotide for reducing STAT3 expression, wherein the oligonucleotide comprises a sense strand comprising the sequence set forth in SEQ ID NO: 1222 and an antisense strand comprising the sequence set forth in SEQ ID NO: 1145, wherein the sense strand and antisense strand form an asymmetric duplex region of 20 nucleotides in length and having an overhang of 2 nucleotides at the 3′ terminus of the antisense strand.
7 . The oligonucleotide of claim 6 , wherein the oligonucleotide reduces expression of STAT3 mRNA in one or more immune cells associated with a tumor microenvironment.
8 . A pharmaceutical composition comprising the oligonucleotide of claim 6 , and a pharmaceutically acceptable carrier, delivery agent, or excipient.
9 . An oligonucleotide for reducing STAT3 expression, wherein the oligonucleotide comprises a sense strand consisting of the sequence set forth in SEQ ID NO: 1222 and an antisense strand consisting of the sequence set forth in SEQ ID NO: 1145, wherein the sense strand and antisense strand form an asymmetric duplex region of 20 nucleotides in length and having an overhang of 2 nucleotides at the 3′ terminus of the antisense strand.
10 . An oligonucleotide for reducing STAT3 expression, wherein the oligonucleotide consists of a sense strand comprising the sequence set forth in SEQ ID NO: 1222 and an antisense strand comprising the sequence set forth in SEQ ID NO: 1145, wherein the sense strand and antisense strand form an asymmetric duplex region of 20 nucleotides in length and having an overhang of 2 nucleotides at the 3′ terminus of the antisense strand.
11 . The oligonucleotide of claim 10 , wherein the oligonucleotide reduces expression of STAT3 mRNA in one or more immune cells associated with a tumor microenvironment.
12 . A pharmaceutical composition comprising the oligonucleotide of claim 10 , and a pharmaceutically acceptable carrier, delivery agent, or excipient.