Method and composition for reducing expression of ROCK-II
Methods and pharmaceutical compositions for treating, and delaying the onset of, viral infection, are provided.
1. A nucleic acid molecule that directs the cleavage of a Rho-associated, coiled-coil containing protein kinase 2 (ROCK-II)-encoding RNA transcript via RNA interference (RNAi), comprising a first nucleotide sequence and a second nucleotide sequence, wherein:
said first nucleotide sequence comprises SEQ ID NO:3;
said second nucleotide sequence is substantially complementary to said first nucleotide sequence; each of said first and second nucleotide sequences is about 21 nucleotides in length; and
said second nucleotide sequence is sufficiently complementary to SEQ ID NO:2 for the nucleic acid molecule to direct cleavage of said ROCK-II-encoding RNA transcript and decrease the expression of ROCK-II via RNAi.
2. The nucleic acid of claim 1 , wherein:
said first nucleotide sequence occurs within a first strand of RNA;
said second nucleotide sequence occurs within a second strand of RNA;
each of said first and second nucleotide sequences is about 21 nucleotides in length; and
said first strand of RNA and said second strand of RNA are annealed to form an intermolecular duplex.
3. A composition comprising the nucleic acid of claim 2 and a pharmaceutically acceptable carrier or diluent.
4. The composition of claim 3 , further comprising an uptake agent.
5. The composition of claim 4 , wherein said uptake agent is selected from LIPOFECTIN®, LIPOFECTAMINE®, or CELLFECTIN®.
6. A modified equivalent of the nucleic acid of claim 2 .
7. A composition comprising the modified equivalent of claim 6 and a pharmaceutically acceptable carrier or diluent.
8. The composition of claim 7 , further comprising an uptake agent.
9. The composition of claim 8 , wherein said uptake agent is selected from LIPOFECTIN®, LIPOFECTAMINE®, or CELLFECTIN®.
10. The nucleic acid of claim 1 , wherein
said first and second nucleotide sequences of RNA each further comprise two 2′-deoxythymidine residues at their 3′ ends, and
said nucleic acid is prepared by the annealing of the nucleic acids of SEQ ID NOs:50 and 51.
11. The nucleic acid of claim 1 , wherein:
said first nucleotide sequence and said second nucleotide sequence occur within a single strand of RNA,
said single strand of RNA is comprised of about 52 nucleotides,
and said first nucleotide sequence and said second nucleotide sequence anneal to form an intramolecular duplex of about 19 basepairs.
12. A composition comprising the nucleic acid of claim 11 and a pharmaceutically acceptable carrier or diluent.
13. The composition of claim 12 , further comprising an uptake agent.
14. The composition of claim 13 , wherein said uptake agent is selected from LIPOFECTIN®, LIPOFECTAMINE®, or CELLFECTIN®.
15. The nucleic acid of claim 11 , wherein said single strand of RNA comprises SEQ ID NO:74.
16. A composition comprising the nucleic acid of claim 15 and a pharmaceutically acceptable carrier or diluent.
17. The composition of claim 16 , further comprising an uptake agent.
18. The composition of claim 17 , wherein said uptake agent is selected from LIPOFECTIN®, LIPOFECTAMINE®, or CELLFECTIN®.