Nucleic acid complexes
The invention relates to nucleic acid complexes, methods of preparation thereof, and uses thereof for delivering a nucleic acid into a cell.
1. A nucleic acid complex comprising a nucleic acid, a macrocyclic compound, and a pendant polymer, wherein the pendant polymer comprises a polymer backbone and is modified with a hydrophobic group, and wherein the macrocyclic compound and the pendant polymer form a host:guest polymer complex.
2. The nucleic acid complex of claim 1 , wherein the nucleic acid is siRNA, miRNA, antisence oligonucleotides, aptamers, or pDNA.
3. The nucleic acid complex of claim 1 , wherein the macrocyclic compound is a modified cyclodextrin.
4. The nucleic acid complex of claim 3 , wherein the modified cyclodextrin is a modified β-cyclodextrin comprising an amino moiety.
5. The nucleic acid complex of claim 1 , wherein the macrocyclic compound is
mono-6-(amino)-6-deoxy-β-cyclodextrin,
mono-6-(N,N′-dimethylethane-1,2-diamine)-6-deoxy-β-cyclodextrin,
mono-6-(N′-(2-aminoethyl)ethane-1,2-diamine)-6-deoxy-β-cyclodextrin,
mono-6-(poly(ethyleneimine)-6-deoxy-β-cyclodextrin
hepta-6-(2′-aminoethyl)amino-β-cyclodextrin,
hepta-6-(2′-hydroxyethylamino)-β-cyclodextrin, or
hepta-6-(hydrazino)-β-cyclodextrin.
6. The nucleic acid complex of claim 1 , wherein the pendant polymer comprises poly(vinyl alcohol), polysaccharide, polyester, or polyamide backbone.
7. The nucleic acid complex of claim 6 , wherein the pendant polymer comprises a poly(ethylene glycol) pendant group.
8. The nucleic acid complex of claim 1 , wherein the hydrophobic group is cholesterol, or a derivative or analog thereof, and wherein said cholesterol, or a derivative or analog thereof, is linked through an acetal linkage to the backbone of the pendant polymer.
9. The nucleic acid complex of claim 1 , wherein the host:guest polymer complex condenses the nucleic acid to form a nanoparticle in a size of from about 120 nm to about 170 nm.
10. A method for delivering a nucleic acid into a cell, the method comprising the step of bringing a nucleic acid complex comprising the nucleic acid into contact with the cell, wherein the nucleic acid complex comprises a nucleic acid, a macrocyclic compound, and a pendant polymer, wherein the pendant polymer is modified with a hydrophobic group, and wherein the macrocyclic compound and the pendant polymer form a host:guest polymer complex.
11. The method of claim 10 , wherein the nucleic acid is siRNA or pDNA.
12. The method of claim 10 , wherein the macrocyclic compound is a modified cyclodextrin.
13. The method of claim 12 , wherein the modified cyclodextrin is a modified β-cyclodextrin comprising an amino moiety.
14. The method of claim 10 , wherein the macrocyclic compound is
mono-6-(amino)-6-deoxy-β-cyclodextrin,
mono-6-(N,N′-dimethylethane-1,2-diamine)-6-deoxy-β-cyclodextrin,
mono-6-(N′-(2-aminoethyl)ethane-1,2-diamine)-6-deoxy-β-cyclodextrin,
hepta-6-(2′-aminoethyl)amino-β-cyclodextrin,
hepta-6-(2′-hydroxyethylamino)-β-cyclodextrin, or
hepta-6-(hydrazino)-β-cyclodextrin.
15. The method of claim 10 , wherein the pendant polymer comprises a poly(vinyl alcohol), polysaccharide, polyester, or polyamide backbone.
16. The method of claim 15 , wherein the pendant polymer comprises a poly(ethylene glycol) pendant group.
17. The method of claim 10 , wherein the hydrophobic group is cholesterol, or a derivative or analog thereof, and wherein said cholesterol, or a derivative or analog thereof, is linked through an acetal linkage to the backbone of the pendant polymer.
18. The method of claim 10 , wherein the host:guest polymer complex condenses the nucleic acid to form a nanoparticle in a size of from about 120 nm to about 170 nm.
19. The method of claim 10 , wherein said cell is in vitro or in vivo.
20. A pharmaceutical composition comprising the nucleic acid complex of claim 1 to produce a pharmaceutical for delivering a nucleic acid into a cell.
21. The nucleic acid complex of claim 1 , wherein the hydrophobic group is adamantane, or a derivative or analog thereof, and wherein said adamantane, or a derivative or analog thereof, is linked through an acetal linkage to the backbone of the pendant polymer.
22. The method of claim 10 , wherein the hydrophobic group is adamantane, or a derivative or analog thereof, and wherein said adamantane, or a derivative or analog thereof, is linked through an acetal linkage to the backbone of the pendant polymer.