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 amcliorating diseases associated with protein or enzyme deficiencies.
1 - 40 . (canceled)
41 . A composition comprising an mRNA encoding an antigen, encapsulated within a lipid nanoparticle,
wherein the lipid nanoparticle has a size less than 150 nm and 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 a molar ratio of greater than 10% of the total lipids in the lipid nanoparticle.
42 . The composition of claim 41 , wherein the lipid nanoparticle comprises cationic lipids at a molar ratio of 20% to 70% of the total lipids.
43 . The composition of claim 42 , wherein the lipid nanoparticle comprises PEG-modified lipids at a molar ratio of 1% to 15% of the total lipids.
44 . The composition of claim 41 , wherein one or more non-cationic lipids comprise DSPC.
45 . The composition of claim 41 , wherein one or more non-cationic lipids comprise DOPE.
46 . The composition of claim 41 , wherein one or more PEG-modified lipids comprise DMG-PEG-2000.
47 . The composition of claim 41 , wherein the mRNA comprises a poly A tail of at least 90 nucleotides.
48 . The composition of claim 47 , wherein the poly A tail comprises at least 200 nucleotides.
49 . The composition of claim 41 , wherein the lipid nanoparticle has a size less than 125 nm.
50 . The composition of claim 49 , wherein the lipid nanoparticle has a size less than 100 nm.
51 . The composition of claim 41 , wherein the mRNA is modified.
52 . The composition of claim 51 wherein the mRNA comprises pseudouridines.
53 . The composition of claim 41 , wherein the mRNA comprises a 5′ UTR.
54 . The composition of claim 41 , wherein the mRNA comprises a 3′ UTR.
55 . The composition of claim 41 , wherein the mRNA comprises a cap structure.
56 . The composition of claim 41 , wherein the antigen is a tumor antigen.
57 . A composition comprising an mRNA encoding an antigen, encapsulated within a lipid nanoparticle, wherein the lipid nanoparticle has a size less than 150 nm and 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 a molar ratio greater than 10% of the total lipids in the lipid nanoparticle, and wherein the mRNA comprises
(i) a 5′-UTR,
(ii) a 3′-UTR,
(iii) a 5′ cap structure, and
(iv) a poly A tail.
58 . The composition of claim 57 , wherein the antigen is a tumor antigen.
59 . A composition comprising an mRNA encoding an antigen, encapsulated within a lipid nanoparticle, wherein the lipid nanoparticle has a size less than 150 nm and 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 a molar ratio greater than 10% of the total lipids in the lipid nanoparticle, and
wherein the mRNA is modified to comprise one or more pseudouridine and the mRNA comprises
(i) a 5′-UTR,
(ii) a 3′-UTR,
(iii) a 5′ cap structure, and
(iv) a poly A tail.
60 . The composition of claim 59 , wherein the antigen is a tumor antigen.