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 IL-12 polypeptide, comprising administering, to a human, a composition comprising an mRNA that encodes the IL-12 polypeptide wherein the mRNA is encapsulated within a lipid nanoparticle, wherein the administering of the composition results in expression of the IL-12 polypeptide encoded by the mRNA that is detectable in a target tissue at least 72 hours after administration, wherein the lipid nanoparticle comprises one or more PEG-modified lipids, and wherein the composition is administered by direct injection into the target tissue.
2. The method of claim 1 , wherein the mRNA comprises a 5′ untranslated region.
3. The method of claim 1 , wherein the mRNA comprises a 3′ untranslated region.
4. The method of claim 3 , wherein the mRNA comprises a cap structure.
5. The method of claim 4 , wherein the mRNA comprises a poly A tail.
6. The method of claim 5 , wherein the lipid nanoparticle comprises one or more cationic lipids.
7. The method of claim 6 , wherein the lipid nanoparticle comprises one or more non-cationic lipids.
8. The method of claim 7 , wherein the mRNA is unmodified.
9. The method of claim 8 , wherein the composition is a reconstituted lyophilized composition.
10. The method of claim 7 , wherein the mRNA comprises a modified nucleotide.
11. The method of claim 10 , wherein the modified nucleotide is pseudouridine.
12. The method of claim 11 , wherein the composition is a reconstituted lyophilized composition.
13. The method of claim 8 , wherein the lipid nanoparticle has a size of less than about 100 nm.
14. The method of claim 11 , wherein the lipid nanoparticle has a size of less than about 100 nm.
15. The method of claim 8 , wherein the one or more PEG-modified lipids constitute from 0.1% to 20% of the total lipids by a molar ratio.
16. The method of claim 11 , wherein the one or more PEG-modified lipids constitute from 0.1% to 20% of the total lipids by a molar ratio.
17. The method of claim 8 , wherein the poly A tail comprises at least 90 nucleotides.
18. The method of claim 11 , wherein the poly A tail comprises at least 500 nucleotides.
19. The method of claim 1 , wherein the target tissue comprises tumor cells.