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US 9,428,535 B2Granted
Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
AssigneeModerna Therapeutics, Inc.
InventorsAntonin de Fougerolles, Atanu Roy, Jason P. Schrum, Suhaib Siddiqi, Paul Hatala, Stephane Bancel
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Abstract
The present disclosure provides methods of increasing the level of a polypeptide of interest in a mammalian subject by administering a polynucleotide having one or more chemical modifications and a Protein:Cytokine ratio of greater than 100.
Claims25
A method of expressing a polypeptide of interest in a mammalian subject comprising administering to said subject an isolated mRNA comprising:
- (a) a sequence of n number of linked nucleosides,
- (b) a 5′ UTR,
- (c) a 3′ UTR, and
- (d) at least one 5′ cap structure,
- wherein said isolated mRNA is fully modified with 1-methylpseudouridine,
- wherein said isolated mRNA, when administered to peripheral blood mononuclear cells provides Protein:Cytokine (P:C) ratios of greater than 100 for TNF-alpha and greater than 100 for IFN-alpha after about eighteen or more hours, and
- wherein said P:C ratios are higher than those of a corresponding mRNA comprising pseudouridine in place of 1-methylpseudouridine.
4 more elements
Dependencies are inferred from the claim text.