Lipid nanoparticle compositions and methods for mRNA delivery
Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.
1. A method for delivery of messenger RNA (mRNA) for in vivo production of a cytokine comprising
administering to a subject a composition comprising an mRNA that encodes the cytokine,
wherein the mRNA is encapsulated within a lipid nanoparticle and
wherein the administering of the composition results in the expression of the cytokine encoded by the mRNA that is detectable in a target tissue at least 48 hours after administration,
wherein the lipid nanoparticle comprises one or more PEG-modified lipids.
2. The method of claim 1 , wherein the lipid nanoparticle comprises one or more cationic lipids and one or more non-cationic lipids.
3. The method of claim 2 , wherein one or more non-cationic lipids comprise DSPC.
4. The method of claim 2 , wherein one or more non-cationic lipids comprise DOPE.
5. The method of claim 2 , wherein the lipid nanoparticle comprises PEG-modified lipids at a molar ratio of 0.5% to 20% of the total lipids.
6. The method of claim 2 , wherein the lipid nanoparticle comprises non-cationic lipids at a molar ratio of 5% to 90% of the total lipids.
7. The method of claim 2 , wherein the lipid nanoparticle comprises cholesterol.
8. The method of claim 1 , wherein one or more PEG-modified lipids comprise DMG-PEG-2000.
9. The method of claim 1 , wherein the cytokine is a tumor necrosis factor.
10. The method of claim 1 , wherein the cytokine is IL-12.
11. The method of claim 1 , wherein the cytokine is IL-23.
12. The method of claim 1 , wherein the composition is administered by local injection.
13. The method of claim 1 , wherein the composition is administered intramuscularly.
14. The method of claim 1 , wherein the composition is administered subcutaneously.
15. The method of claim 1 , wherein the target tissue comprises tumor cells.
16. The method of claim 1 , wherein the target tissue comprises muscle cells.
17. The method of claim 16 , wherein the muscles cells are skeletal muscle cells, or vascular smooth muscle cells.
18. The method of claim 1 , wherein the mRNA is modified.
19. The method of claim 18 , wherein the mRNA comprises pseudouridines.
20. The method of claim 1 , wherein the mRNA comprises a 3′ untranslated region.
21. The method of claim 1 , wherein the mRNA comprises a cap structure.
22. The method of claim 1 , wherein the mRNA comprises a poly A tail.
23. The method of claim 1 , wherein the lipid nanoparticle has a size of less than 150 nm.
24. The method of claim 23 , wherein the lipid nanoparticle has a size of less than 125 nm.
25. The method of claim 24 , wherein the lipid nanoparticle has a size of less than 100 nm.