Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
AssigneeModernaTX, Inc.
InventorsAntonin De Fougerolles, Justin Guild
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Abstract
The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.
Claims19
A method of expressing a polypeptide in a mammalian subject, the method comprising administering to the subject a pharmaceutical composition comprising a plurality of lipid nanoparticles encapsulating a polynucleotide, wherein the lipid nanoparticles comprise a cationic lipid, a neutral lipid, cholesterol, and a PEGylated lipid, wherein the plurality of lipid nanoparticles has a mean particle size of from 80 nm to 160 nm, and
- wherein the polynucleotide comprises:
- (a) an open reading frame encoding the polypeptide and consisting of nucleosides selected from uridine, cytidine, adenosine, and guanosine;
- (b) a 5′-UTR;
- (c) a 5′ cap structure;
- (d) a 3′-UTR;
- and
- (e) a 3′ tailing sequence of linked nucleosides.
Dependencies are inferred from the claim text.