Compositions and methods for inhibiting expression of the LECT2 gene
The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the LECT2 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of LECT2.
1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of LECT2, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a LECT2 RNA transcript, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the antisense sequence and all the modifications of SEQ ID NO: 93 or 290 and the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the sense sequence and all the modifications of SEQ ID NO: 92 or 289.
2. The dsRNA of claim 1 , wherein the dsRNA comprises a duplex region that is 15-30 nucleotide pairs in length.
3. The dsRNA of claim 1 , wherein the region of complementarity is at least 17 nucleotides in length.
4. The dsRNA of claim 1 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide.
5. The dsRNA of claim 1 , wherein the dsRNA comprises a duplex region that is 17-23 nucleotide pairs in length.
6. The dsRNA of claim 1 , wherein the dsRNA comprises a duplex region that is 19-21 nucleotide pairs in length.
7. The dsRNA of claim 1 , wherein the dsRNA comprises a duplex region that is 21-23 nucleotide pairs in length.
8. The dsRNA of claim 1 , wherein at least one strand comprises a 3′ overhang of at least 2 nucleotides.
9. The dsRNA of claim 1 , wherein the region of complementarity is 19 nucleotides in length.
10. The dsRNA of claim 1 , wherein the region of complementarity is between 19 and 21 nucleotides in length.
11. The dsRNA of claim 1 , wherein
(a) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 92 and the antisense strand comprises the sequence and all the modification of SEQ ID NO: 93; or
(b) the sense strand comprises the sequence and all the modifications of SEQ ID NO: 289 and the antisense strand comprises the sequence and all the modification of SEQ ID NO: 290.
12. The dsRNA of claim 1 , wherein the sense strand is conjugated to at least one ligand.
13. The dsRNA of claim 12 , wherein the ligand is a GalNAc ligand.
14. The dsRNA of claim 12 , wherein the ligand is
15. The dsRNA of claim 12 , wherein the ligand is attached via a linker.
16. The dsRNA of claim 15 , wherein the ligand and linker are as shown in Formula XXIV:
17. A pharmaceutical composition for inhibiting expression of a LECT2 gene, the composition comprising the dsRNA of claim 1 .
18. An isolated cell containing the dsRNA of claim 1 .
19. A vector encoding at least one strand of the dsRNA of claim 1 .
20. An isolated cell comprising the vector of claim 19 .