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 composition comprising: a first messenger RNA (mRNA) encoding a protein or peptide and a second mRNA encoding a protein or peptide, wherein the first mRNA and the second mRNA are encapsulated within a lipid nanoparticle,
wherein the lipid nanoparticle has a size less than 150 nm and comprises:
(i) a PEG-modified lipids at a molar ratio of greater than 1% of the total lipids in the lipid nanoparticle,
(ii) a cationic lipids at a molar ratio of greater than 10% of the total lipids in the lipid nanoparticle,
(iii) a non-cationic lipids at a molar ratio of greater than 5% of the total lipids in the lipid nanoparticle, and
(iv) cholesterol at a molar ratio of greater than 10% of the total lipids in the lipid nanoparticle.
2. The composition of claim 1 , wherein the lipid nanoparticle comprises PEG-modified lipids at a molar ratio of 0.5% to 20% of the total lipids.
3. The composition of claim 2 , wherein PEG-modified lipids comprise DMG-PEG-2000.
4. The composition of claim 1 , wherein the lipid nanoparticle comprises cationic lipids at a molar ratio of 20% to 70% of the total lipids.
5. The composition of claim 1 , wherein the lipid nanoparticle comprises non-cationic lipids at a molar ratio of greater than 5% to less than 90% of the total lipids.
6. The composition of claim 5 , wherein non-cationic lipids comprise DSPC.
7. The composition of claim 5 , wherein non-cationic lipids comprise DOPE.
8. The composition of claim 1 , wherein the first mRNA comprises:
(i) a 5′-UTR,
(ii) a 3′-UTR,
(iii) a 5′ cap structure, and
(iv) a poly A tail.
9. The composition of claim 8 , wherein the poly A tail comprises at least 90 nucleotides.
10. The composition of claim 8 , wherein the poly A tail comprises at least 200 nucleotides.
11. The composition of claim 1 , wherein the first mRNA is modified.
12. The composition of claim 11 , wherein the first mRNA comprises pseudouridine.
13. The composition of claim 1 , wherein the lipid nanoparticle has a size less than 125 nm.
14. The composition of claim 1 , wherein the lipid nanoparticle has a size less than 100 nm.
15. The composition of claim 8 , wherein the second mRNA comprises:
(i) a 5′-UTR,
(ii) a 3′-UTR,
(iii) a 5′ cap structure, and
(iv) a poly A tail.
16. The composition of claim 15 , wherein the poly A tail comprises at least 90 nucleotides.
17. The composition of claim 15 , wherein the poly A tail comprises at least 200 nucleotides.
18. The composition of claim 8 , wherein the second mRNA is modified.
19. The composition of claim 18 , wherein the second mRNA comprises pseudouridine.