Complexes of small-interfering nucleic acids
View Patent ↗The present invention relates to complexes of small-interfering nucleic acids (siNA). Compositions of siNA suited for administration to a patient are described. Methods for delivering the compositions are also described.
1. A complex comprising a chitosan complexed with a siNA, wherein; (i) the chitosan is attached through an amide-containing linkage to a water-soluble polymer, wherein the water-soluble polymer is a polyethylene oxide having a weight-average molecule weight in the range of from about 10,000 Daltons to about 85,000 Daltons and end-capped with a C 1-6 alkoxy group; and (ii) the chitosan has a molecular weight of between 1,000 Daltons and 2,000,000 Daltons.
2. The complex of claim 1 , wherein the chitosan has a molecular weight of between 1,000 Daltons and 25,000 Daltons.
3. The complex of claim 1 , wherein the chitosan has a degree of deacetylation (% DA) of 50 to 100%.
4. The complex of claim 1 , wherein more than one water-soluble polymer is attached to the chitosan.
5. The complex of claim 1 , wherein the siNA is selected from the group consisting of siRNA, miRNA and shRNA.
6. The complex of claim 5 , wherein the siNA is a siRNA.
7. The complex of claim 1 , wherein the siNA has a length of from 10 to 30 nucleotides.
8. The complex of claim 1 , wherein the siNA has a length of from 15 to 25 nucleotides.
9. The complex of claim 1 , wherein the siNA is a single stranded siNA.
10. The complex of claim 1 , wherein the siNA is a double stranded siNA.
11. The complex of claim 10 , wherein the double stranded siNA is blunt ended.
12. The complex of claim 10 , wherein the double stranded siNA has a 5′ overhang.
13. The complex of claim 12 , wherein the 5′ overhang is an overhang of a number of nucleotides selected from the group consisting of 1, 2, 3 and 4.
14. The complex of claim 10 , wherein the double stranded siNA has a 3′ overhang.
15. The complex of claim 14 , wherein the 3′ overhang is an overhang of a number of nucleotides selected from the group consisting of 1, 2, 3 and 4.
16. The complex of claim 1 , wherein the siNA is a triple stranded siNA.
17. The complex of claim 1 , wherein the siNA includes one or more modified nucleotides selected from the group consisting of 2′ O-methyl nucleotides, 2′ F nucleotides, 2′-deoxynucleotides, 2′-O-methoxyethyl (2′-O-MOE) nucleotides, locked nucleic acids and unlocked nucleic acids.
18. The complex of claim 1 , further comprising a targeting moiety attached to one component of the complex.
19. The complex of claim 18 , wherein the targeting moiety is selected from the group consisting of folate, pemetrexed, RGD peptide, and cholesterol.
20. A composition comprising the complex of claim 1 .
21. The composition of claim 20 , further comprising a transfection agent.
22. A method comprising subcutaneously administering to a patient the complex of claim 1 .