Conjugates of small-interfering nucleic acids
View Patent ↗The present invention relates to conjugates 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 conjugate comprising a residue of a siNA having a 5′ amino linker with a terminal amino group having the structure
covalently attached at the terminal amino group to a single polymeric reagent having the following structure,
wherein: R 2 is H and each of R 1 and R 3 is
R 2 is H and each of R 1 and R 3 is
R 1 is H, R 2 is
and R 3 is
R 1 is H, R 2 is
and R 3 is
where each m-PEG represents CH 3 O(CH 2 CH 2 O) n —CH 2 CH 2 ˜ and (n) is defined to provide CH 3 O(CH 2 CH 2 O) n —CH 2 CH 2 ˜ with a weight-average molecular weight of from 10,000 Daltons to 40,000 Daltons
, and wherein the siNA is selected from the group consisting of double stranded siNA that is blunt ended, double stranded siNA that has a 5′overhang, and double stranded siNA that has a 3′ overhang.
2. The conjugate of claim 1 , wherein the siNA is a siRNA.
3. The conjugate of claim 1 , wherein the siNA has a length of from 10 to 30 nucleotides.
4. The conjugate of claim 1 , wherein the siNA has a length of from 15 to 25 nucleotides.
5. The conjugate of claim 1 , wherein the siNA is double stranded siNA that is blunt ended.
6. The conjugate of claim 1 , wherein the siNA is double stranded siNA that has a 5′overhang.
7. The conjugate of claim 6 , wherein the 5′overhang is an overhang of a number of nucleotides selected from the group consisting of 1, 2, 3 and 4.
8. The conjugate of claim 1 , wherein the siNA is a double stranded siNA that has a 3′overhang.
9. The conjugate of claim 8 , wherein the 3′overhang is an overhang of a number of nucleotides selected from the group consisting of 1, 2, 3 and 4.
10. The conjugate 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′OMOE nucleotides, locked nucleic acids and unlocked nucleic acids.