Granted Patent
B2
US 12,636,304 · App. 17/235,535 · Granted May 26, 2026
Metabolically stabilized double stranded mRNA
Assignee:
University of Iowa Research Foundation
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Abstract
Double stranded mRNA, e.g., produced in vitro, as well as method of making and using the ds mRNA, are provided. For example, the disclosure provides a method of expressing a prophylactic or therapeutic protein in mammalian cells in vivo, that includes introducing a composition comprising ds mRNA that encodes a protein to the mammalian cells in an amount effective to express the protein in vivo.
Claims (19)
1 . A method to induce an immune response in a mammal, comprising:
administering to the mammal a composition comprising a double-stranded (ds) mRNA encoding a protein, wherein the protein is an antigen, wherein the ds mRNA comprises a forward strand and a reverse strand, wherein the forward strand of the ds mRNA has a 5′ cap, a start codon, a poly A sequence and encodes the protein, wherein the reverse strand comprises a 5′ amino allyl modified uridine or cytidine, wherein the 5′ amino allyl modified uridine or cytidine is functionalized with an anhydride, or an N-hydroxysuccinamide ester, wherein the two strands of the ds mRNA are hydrogen bonded over at least 50% of the length of the strands, wherein the hydrogen bonded strands include at least a portion of the coding region for the protein;
wherein following administration of the composition to the mammal, the mammal expresses the protein, and wherein the protein induces an immune response in the mammal;
wherein the composition further comprises a carrier protein or a synthetic polymer.
2 . The method of claim 1 , wherein the protein is a cancer antigen.
3 . The method of claim 1 , wherein the composition is systemically administered to the mammal.
4 . The method of claim 1 , wherein the composition further comprises a liposome or a nanoparticle.
5 . The method of claim 1 , wherein at least one strand includes one or more non-natural nucleotides.
6 . The method of claim 5 , wherein at least one of the non-natural nucleotides has a non-natural sugar or a non-natural nucleobase, or a combination thereof.
7 . The method of claim 5 , wherein at least 5% of the nucleotides are non-natural nucleotides.
8 . The method of claim 5 , wherein the non-natural nucleotide is a purine analog.
9 . The method of claim 1 , wherein at least one strand includes at least one non-phosphodiester bond.
10 . The method of claim 1 , wherein at least one strand includes 5-formyl cytidine or pseudouridine.
11 . The method of claim 1 , wherein one of the strands is no more than 5 kb in length.
12 . The method of claim 1 , wherein at least one strand has two or more different non-natural nucleotides.
13 . The method of claim 1 , wherein the strands are not the same length.
14 . The method of claim 1 , wherein the composition is administered intramuscularly (IM).
15 . The method of claim 1 , wherein the protein is a viral antigen.
16 . The method of claim 1 , wherein the protein is a bacterial antigen.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 20, 2021
From: RICE, KEVIN G.; CROWLEY, SAMUEL T.
To: UNIVERSITY OF IOWA RESEARCH FOUNDATION
Reel/Frame 055978/0069 →
Continuity (4)
Division
16090468
Provisional Application
62317142
· Apr 1, 2016
Provisional Application
62335186
· Apr 1, 2016
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