Compositions and methods for inhibiting expression of CD274/PD-L1 gene
View Patent ↗The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the CD274/PD-L1 gene, and methods of using such dsRNA compositions to inhibit expression of CD274/PD-L1.
1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of CD274/PD-L1, wherein said dsRNA comprises a sense strand and an antisense strand, wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO: 415 and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the corresponding antisense nucleotide sequence of SEQ ID NO: 416, and wherein each said strand is no more than 30 nucleotides in length.
2. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of CD274/PD-L1, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a CD274/PD-L1 RNA transcript, which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the antisense sequence of SEQ ID NO: 416, and wherein each said strand is no more than 30 nucleotides in length.
3. The dsRNA of claim 2 , wherein said dsRNA comprises at least one modified nucleotide.
4. The dsRNA of claim 3 , wherein at least one of said modified nucleotides is chosen from the group consisting of: a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.
5. The dsRNA of claim 3 , wherein said modified nucleotide is chosen from the group consisting of: a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.
6. The dsRNA of a claim 2 , wherein the region of complementarity is between 19 and 21 nucleotides in length.
7. The dsRNA of claim 6 , wherein the region of complementarity is 19 nucleotides in length.
8. The dsRNA of claim 2 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide.
9. The dsRNA of claim 2 , wherein at least one strand comprises a 3′ overhang of at least 2 nucleotides.
10. The dsRNA of claim 2 , further comprising a ligand.
11. The dsRNA of claim 2 , wherein the region of complementarity consists of the antisense sequence of SEQ ID NO: 416.
12. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of CD274/PD-L1, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a CD274/PD-L1 RNA transcript, which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the antisense sequence consisting of SEQ ID NO: 416 and wherein the sense strand consists of SEQ ID NO: 415.
13. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of CD274/PD-L1, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a CD274/PD-L1 RNA transcript, which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the antisense sequence consisting of SEQ ID NO: 416 and wherein the dsRNA comprises a sense strand consisting of a sense strand sequence of SEQ ID NO: 415.
14. A cell containing the dsRNA of claim 2 .
15. The dsRNA of claim 2 , further comprising a pharmaceutically acceptable carrier.
16. A vector encoding the dsRNA of claim 1 , 2 , 12 , or 13 .