Serpina1 siRNAs: compositions of matter and methods of treatment
View Patent ↗The technology described herein relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the Serpina1 gene, and methods of using such dsRNA compositions to inhibit expression of Serpina1.
1. A method of inhibiting Serpina1 expression in a cell, the method comprising:
(a) introducing into the cell a double-stranded ribonucleic acid (dsRNA) comprising a sense strand having the sequence of SEQ ID NO: 129 and an antisense strand having the sequence of SEQ ID NO: 173; and
(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a Serpina1 gene, thereby inhibiting expression of the Serpina1 gene in the cell.
2. The method of claim 1 , wherein the Serpina1 expression is inhibited by at least 30%.
3. A method of treating a disorder mediated by Serpina1 expression comprising administering to a patient in need of such treatment a therapeutically effective amount of a double-stranded ribonucleic acid (dsRNA) comprising a sense strand having the sequence of SEQ ID NO: 129 and an antisense strand having the sequence of SEQ ID NO: 173.
4. The method of claim 3 , wherein the disorder is Alpha 1 anti-trypsin deficiency liver disease.
5. The method of claim 3 , wherein the administration of the dsRNA to the subject causes a decrease in cirrohsis, fibrosis, and/or Serpina1 protein accumulation in the liver.
6. The method of claim 3 , wherein the likelihood of hepatocellular carcinoma occurring in the patient is reduced.
7. The method of claim 3 , wherein the dsRNA is administered at a concentration of 0.01 mg/kg-5 mg/kg bodyweight of the patient.