Cochleate compositions directed against expression of proteins
View Patent ↗Disclosed herein are novel siRNA-cochleate and morpholino-cochleate compositions. Also disclosed are methods of making and using siRNA-cochleate and morpholino-cochleate compositions.
1. An siRNA-cochleate composition comprising:
a cochleate; and
an siRNA associated with the cochleate,
wherein the cochleate comprises a negatively charged lipid component and a multivalent cation component,
wherein the siRNA is complexed with polyethylenimine (PEI) prior to contacting a liposome.
2. The siRNA-cochleate composition of claim 1 , wherein the siRNA comprises at least one mismatch.
3. The siRNA-cochleate composition of claim 1 , wherein the siRNA comprises at least one substitution.
4. The siRNA-cochleate composition of claim 1 , wherein the siRNA is about 21-23 nucleotides long.
5. The siRNA-cochleate composition of claim 1 , wherein the siRNA mediates RNA interference against a target mRNA.
6. The siRNA-cochleate composition of claim 5 , wherein the target mRNA expresses a protein selected from the group consisting of: a cancer protein, a virus protein, an HIV protein, a fungus protein, a bacterial protein, an abnormal cellular protein, a normal cellular protein.
7. The siRNA-cochleate composition of claim 1 , further comprising a second siRNA directed against a second target mRNA.
8. The siRNA-cochleate composition of claim 1 , further comprising at least one additional cargo moiety.
9. The siRNA-cochleate composition of claim 1 , further comprising an aggregation inhibitor.
10. A method of forming an siRNA-cochleate composition comprising:
complexing an siRNA with
polyethylenimine (PEI);
contacting the complexed siRNA with a liposome; and
precipitating the liposome and the complexed siRNA to form an siRNA-cochleate composition,
wherein the cochleate comprises a negatively charged lipid component and a multivalent cation component.
11. The method of claim 10 , comprising adjusting the pH of a liposomal suspension of the siRNA.
12. The method of claim 10 , comprising charging the base pairs of the siRNA.
13. The method of claim 10 , comprising using an elevated amount of calcium for precipitating the liposome and the siRNA.
14. The method of claim 10 , comprising the step of extruding the liposome and the siRNA prior to precipitation.