Lipid formulated compositions and methods for inhibiting expression of serum amyloid A gene
View Patent ↗The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a Serum Amyloid A (SAA) gene, and methods of using the dsRNA to inhibit expression of SAA.
1. A double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand 15-30 nucleotides in length and an antisense strand 15-30 nucleotides in length, the antisense strand comprising a region of complementarity which is complementary to SEQ ID NO: 225, and wherein said region of complementarity is less than 30 nucleotides in length, and at least 15 nucleotides in length.
2. The dsRNA of claim 1 , wherein the sense strand comprises 15 or more contiguous nucleotides of the nucleotide sequence of SEQ ID NO:225.
3. The dsRNA of claim 1 , wherein the antisense strand comprises 15 or more contiguous nucleotides of the nucleotide sequence of SEQ ID NO:226.
4. The dsRNA of claim 1 , wherein the sense strand comprises the nucleotide sequence of SEQ ID NO:225 and the antisense strand comprises the nucleotide sequence of SEQ ID NO:226.
5. The dsRNA of claim 1 , wherein the sense strand consists of SEQ ID NO:69 and the antisense strand consists of SEQ ID NO:70 and said sense strand is modified as follows to include a 2′-O-methylcytidine-3′-phosphate as indicated by a lower case letter “c” and a 2′-O-methyluridine-3′-phosphate as indicated by a lower case letter “u”: SEQ ID NO:69: GccGAAGcuucuuuucGuudTdT.
6. The dsRNA of claim 1 , wherein said dsRNA comprises at least one modified nucleotide.
7. The dsRNA of claim 6 , wherein at least one of said modified nucleotides is chosen from the group 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.
8. The dsRNA of claim 6 , wherein said modified nucleotide is chosen from the group 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.
9. The dsRNA of claim 1 , wherein the dsRNA is conjugated to a ligand.
10. The dsRNA of claim 1 , wherein the dsRNA is formulated in a lipid formulation.
11. The dsRNA of claim 1 , wherein the dsRNA has an IC50 of less than 10 pM.
12. A cell containing the dsRNA of claim 1 .
13. A pharmaceutical composition for inhibiting expression of an SAA gene comprising the dsRNA of claim 1 .
14. A method of inhibiting SAA expression in a cell, the method comprising:
(a) introducing into the cell the dsRNA of claim 1 ; and
(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of an SAA gene, thereby inhibiting expression of the SAA gene in the cell.
15. A vector comprising a nucleotide sequence that encodes at least one strand of the dsRNA of claim 1 .
16. A cell comprising the vector of claim 15 .
17. A pharmaceutical composition for inhibiting expression of an SAA gene comprising the dsRNA of claim 5 .
18. A method of inhibiting SAA expression in a cell, the method comprising:
(a) introducing into the cell the dsRNA of claim 5 ; and
(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of an SAA gene, thereby inhibiting expression of the SAA gene in the cell.