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 protein or a peptide comprising
administering to a subject a composition comprising an mRNA that encodes the protein or the peptide, wherein the mRNA is encapsulated within a lipid nanoparticle and
wherein the administering of the composition results in the expression of the protein or the peptide encoded by the mRNA, wherein the lipid nanoparticle comprises
(i) a PEG-modified lipid at a molar ratio of greater than 1% of the total lipids in the lipid nanoparticle,
(ii) a cationic lipid at a molar ratio of greater than 10% of the total lipids in the lipid nanoparticle,
(iii) a non-cationic lipid at a molar ratio of greater than 5% of total lipids in the lipid nanoparticle, and
(iv) cholesterol at greater than 10% of the total lipids in the lipid nanoparticle
wherein the non-cationic lipid comprises DOPE or DSPC.
2. The method of claim 1 , wherein the non-cationic lipid comprises DSPC.
3. The method of claim 2 , wherein the lipid nanoparticle comprises PEG-modified lipids at a molar ratio of 1% to 20% of the total lipids.
4. The method of claim 3 , wherein the lipid nanoparticle comprises non-cationic lipids at a molar ratio of 5% to 90% of the total lipids.
5. The method of claim 1 , wherein the non-cationic lipid comprises DOPE.
6. The method of claim 5 , wherein one or more PEG-modified lipids comprise DMG-PEG-2000.
7. The method of claim 1 , wherein the composition is administered systemically.
8. The method of claim 1 , wherein the composition is administered intramuscularly.
9. The method of claim 1 , wherein the composition is administered subcutaneously.
10. The method of claim 1 , wherein the administering of the composition results in the expression of the protein or the peptide encoded by the mRNA that is detectable in a target tissue at least 48 hours after administration.
11. The method of claim 1 , wherein the mRNA is modified.
12. The method of claim 11 , wherein the mRNA comprises pseudouridines.
13. The method of claim 1 , wherein the mRNA comprises a 3′ untranslated region.
14. The method of claim 1 , wherein the mRNA comprises a cap structure.
15. The method of claim 1 , wherein the mRNA comprises a poly A tail.
16. The method of claim 1 , wherein the lipid nanoparticle has a size of less than 150 nm.
17. The method of claim 16 , wherein the lipid nanoparticle has a size of less than 125 nm.
18. The method of claim 17 , wherein the lipid nanoparticle has a size of less than 100 nm.
19. The method of claim 1 , wherein the administering of the composition confers immunity to a subject.
20. The method of claim 1 , wherein the target tissue comprises muscle cells.
21. The method of claim 20 , wherein the muscles cells are skeletal muscle cells, or vascular smooth muscle cells.