RNA containing modified nucleosides and methods of use thereof
AssigneeThe Trustees of the University of Pennsylvania
InventorsKatalin Kariko, Drew Weissman
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Abstract
This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.
Claims15
A method for reducing the immunogenicity of in vitro-synthesized RNA comprising an open reading frame that encodes a functional protein, the method comprising:
- replacing a nucleotide of the in vitro-synthesized RNA with at least one modified nucleotide comprising a modified nucleoside selected from the group consisting of:
- pseudouridine (Ψ), 1-methylpseudouridine (m1Ψ), 5-methyluridine (m5U), 2-thiouridine (s2U), 2′-O-methyl-U (Um) and 5-methylcytidine (m5C),
- wherein when pseudouridine (Ψ) is selected, it replaces uridine, and
- wherein when 1-methylpseudouridine (m1Ψ) is selected, it replaces uridine, and
- wherein when 5-methyluridine (m5U) is selected, it replaces uridine, and
- wherein when 2-thiouridine (s2U) is selected, it replaces uridine, and
- wherein when 2′-O-methyl-U (Um) is selected, it replaces uridine, and
- wherein when 5-methylcytidine (m5C) is selected, it replaces cytidine, and
- thereby generating in vitro-synthesized RNA comprising a modified nucleotide and reducing the immunogenicity of said in vitro-synthesized RNA compared with an in vitro-synthesized RNA that does not comprise said modified nucleotide.
Dependencies are inferred from the claim text.