Modified nucleosides, nucleotides, and nucleic acids, and uses thereof

摘要

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.

主权项

1. 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.