IP Library Granted Patent US 8,058,257
Granted Patent B2
US 8,058,257 · App. 12/720,465 · Granted Nov 15, 2011

Compositions and methods for inhibiting expression of a gene from the JC virus

Assignee: Alnylam Pharmaceuticals, Inc.
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Quick Facts
Patent No.
US 8,058,257
App. No.
12/720,465
Granted
Nov 15, 2011
Kind
B2
Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a gene from the JC Virus (JC virus genome), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of a gene from the JC Virus. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by JC virus expression and the expression of a gene from the JC Virus using the pharmaceutical composition; and methods for inhibiting the expression of a gene from the JC Virus in a cell.

Claims (20)

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a human JC virus genome in a cell, wherein said dsRNA comprises a sense strand and an antisense strand that together form a region of complementarity, and wherein said sense strand consists of UGUUGAAUGUUGGGUUCCUTT (SEQ ID NO: 936) and said antisense strand consists of AGGAACCCAACAUUCAACATT (SEQ ID NO: 937).

2. The dsRNA of claim 1 , wherein at least one nucleotide of said sense strand or said antisense strand is a modified nucleotide.

3. The dsRNA of claim 2 , wherein said modified nucleotide 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.

4. The dsRNA of claim 2 , 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.

5. A cell comprising the dsRNA of claim 1 .

6. A pharmaceutical composition for inhibiting the expression of a gene from a JC Virus in an organism, comprising the dsRNA of claim 1 and a pharmaceutically acceptable carrier.

7. The pharmaceutical composition of claim 6 , wherein the pharmaceutically acceptable carrier comprises a lipid.

8. A method for inhibiting the expression of a gene from a JC Virus 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 a gene from a JC Virus, thereby inhibiting expression of a gene from a JC Virus in the cell.

9. A method of inhibiting replication of a JC virus in a patient comprising administering to the patient an amount of the dsRNA of claim 1 effective to inhibit replication of the virus.

10. A vector for inhibiting the expression of a gene from a JC Virus in a cell, said vector being capable of a) expressing the dsRNA of claim 1 as a single RNA molecule with two complementary regions; or alternatively b) expressing each strand of the dsRNA of claim 1 under the control of a separate promoter.

11. A cell comprising the vector of claim 10 .

12. The dsRNA of claim 1 , wherein said sense strand consists of uGuuGAAuGuuGGGuuccuTsT (SEQ ID NO: 131), and wherein said antisense strand consists of AgGAACCcAAcAUUcAAcATsT (SEQ ID NO:132), wherein u is a uridine ribonucleotide having a 2′-O-methyl modification, and wherein c is a cytidine ribonucleotide having a 2′-O-methyl modification, and wherein g is a guanosine ribonucleotide having a 2′-O-methyl modification and s is a phosphorothioate between nucleotides 20 and 21.

13. A pharmaceutical composition for inhibiting the expression of a gene from a JC Virus in an organism, comprising the dsRNA of claim 12 and a pharmaceutically acceptable carrier.

14. The pharmaceutical composition of claim 13 , wherein the pharmaceutically acceptable carrier comprises a lipid.

15. A method for inhibiting the expression of a gene from a JC Virus in a cell, the method comprising:

(a) introducing into the cell the dsRNA of claim 12 ; and

(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a gene from a JC Virus, thereby inhibiting expression of a gene from a JC Virus in the cell.

16. A method of inhibiting replication of a JC virus in a patient comprising administering to the patient an amount of the dsRNA of claim 12 effective to inhibit replication of the virus.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 16, 2010
From: BRAMLAGE, BIRGIT
To: ALNYLAM EUROPE AG
Reel/Frame 024088/0488 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2010
From: ALNYLAM EUROPE AG
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 024053/0706 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2010
From: SAH, DINAH
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 024053/0715 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2010
From: BRAMLAGE, BIRGIT
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 024053/0735 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2010
From: TAN, PAMELA
To: ALNYLAM EUROPE AG
Reel/Frame 024053/0743 →
Continuity (3)
Continuation 11741205 · Apr 27, 2007
Provisional Application 60795765 · Apr 28, 2006
Related Publication 20100227915A1 · Sep 9, 2010