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 - 40 . (canceled)
41 . A method of delivery of messenger RNA (mRNA) comprising
administering to a subject in need of delivery a composition comprising a therapeutic first mRNA that encodes an enzyme and is encapsulated within a lipid nanoparticle and
wherein the administering of the composition results in the expression of the enzyme encoded by the mRNA that is detectable in serum at least 48 hours after administration, wherein the lipid nanoparticle comprises one or more PEG-modified lipids.
42 . The method of claim 41 , wherein the lipid nanoparticle comprises one or more cationic lipids and one or more non-cationic lipids.
43 . The method of claim 42 , wherein one or more non-cationic lipids comprise DSPC.
44 . The method of claim 42 , wherein one or more non-cationic lipids comprise DOPE.
45 . The method of claim 42 , wherein the lipid nanoparticle comprises PEG-modified lipids at a molar ratio of 0.5% to 20% of the total lipids.
46 . The method of claim 42 , wherein the lipid nanoparticle comprises non-cationic lipids at a molar ratio of 5% to 90% of the total lipids.
47 . The method of claim 42 , wherein the lipid nanoparticle comprises cholesterol.
48 . The method of claim 41 , wherein one or more PEG-modified lipids comprise DMG-PEG-2000.
49 . The method of claim 41 , wherein the administration of the composition results in deactivation or knocking-down a malfunctioning endogenous protein.
50 . The method of claim 41 , wherein the composition comprises a second nucleic acid that facilitates the function of the therapeutic first mRNA encapsulated within the lipid nanoparticle.
51 . The method of claim 41 , wherein the composition is administered systemically.
52 . The method of claim 41 , wherein the composition is administered intravenously.
53 . The method of claim 41 , wherein the composition is administered intramuscularly.
54 . The method of claim 41 , wherein the composition is administered subcutaneously.
55 . The method of claim 41 , wherein the mRNA is modified.
56 . The method of claim 55 , wherein the mRNA comprises pseudouridines.
57 . The method of claim 41 , wherein the mRNA comprises a 3′ untranslated region.
58 . The method of claim 41 , wherein the mRNA comprises a cap structure.
59 . The method of claim 41 , wherein the mRNA comprises a poly A tail.
60 . The method of claim 41 , wherein the lipid nanoparticle has a size of less than 150 nm.
61 . The method of claim 60 , wherein the lipid nanoparticle has a size of less than 125 nm.
62 . The method of claim 60 , wherein the lipid nanoparticle has a size of less than 100 nm.