IP Library › Granted Patent US 12,241,063
Granted Patent B2
US 12,241,063 · App. 17/933,500 · Granted Mar 4, 2025

Modified messenger RNA comprising functional RNA elements

Inventors: Melissa J. Moore (Cambridge, MA); Caroline Köhrer (Cambridge, MA); Ruchi Jain (Cambridge, MA); Vladimir Presnyak (Cambridge, MA)
Assignee: ModernaTX, Inc.
C12N15/11A61K47/6929C12N15/85C12N15/88C12N2310/321C12N2310/322C12N2310/335
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Quick Facts
Patent No.
US 12,241,063
App. No.
17/933,500
Granted
Mar 4, 2025
Kind
B2
Abstract

The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

Claims (34)

1. A method of expressing a messenger RNA (mRNA) in a cell, comprising contacting the cell with the mRNA, wherein the mRNA comprises

(i) a 5′ untranslated region (UTR) comprising an RNA element as set forth in SEQ ID NO: 2; and

(ii) an open reading frame comprising an initiation codon and encoding a polypeptide;

wherein the RNA element has a 3′end located 10-20 nucleotides or 6-10 nucleotides upstream of the initiation codon in the 5′UTR, and

wherein the mRNA comprises one or more chemically modified nucleotides,

thereby expressing the mRNA in the cell.

2. The method of claim 1 , wherein the RNA element has a 3′ end located 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides upstream of the initiation codon.

3. The method of claim 1 , wherein the mRNA comprises a 5′ cap, a 3′ UTR, and a poly A tail.

4. The method of claim 1 , wherein the mRNA comprises one or more pseudouridines or pseudouridine analogs.

5. The method of claim 1 , wherein the mRNA is fully modified with N1-methylpseudouridine.

6. The method of claim 1 , wherein the mRNA is formulated in a lipid nanoparticle.

7. A method of expressing a mRNA in a cell, comprising contacting the cell with the mRNA, wherein the mRNA comprises

(i) a 5′UTR comprising an RNA element inserted into the nucleotide sequence set forth in SEQ ID NO: 33, and

(ii) an open reading frame comprising an initiation codon and encoding a polypeptide;

wherein the RNA element is CCCCGGCGCC (SEQ ID NO: 2),

wherein the RNA element has a 3′end located 10-20 nucleotides or 6-10 nucleotides upstream of the initiation codon in the 5′UTR, and

wherein the mRNA comprises one or more chemically modified nucleotides,

thereby expressing the mRNA in the cell.

8. The method of claim 7 , wherein the RNA element has a 3′end located 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides upstream of the initiation codon.

9. The mRNA of claim 7 , wherein the mRNA comprises a 5′ cap, a 3′ UTR, and a poly A tail.

10. The mRNA of claim 7 , wherein the mRNA comprises one or more pseudouridines or pseudouridine analogs.

11. The mRNA of claim 7 , wherein the mRNA is fully modified with N1-methylpseudouridine.

12. The method of claim 7 , wherein the mRNA is formulated in a lipid nanoparticle.

13. A method of expressing a mRNA in a cell, comprising contacting the cell with the mRNA, wherein the mRNA comprises

(i) a 5′UTR comprising a nucleotide sequence as set forth in SEQ ID NO: 34;

(ii) an open reading frame comprising an initiation codon and encoding a polypeptide; and

wherein the mRNA comprises one or more chemically modified nucleotides,

thereby expressing the mRNA in the cell.

14. The method of claim 13 , wherein the mRNA comprises a 5′ cap, a 3′ UTR, and a poly A tail.

15. The method of claim 13 , wherein the mRNA comprises one or more pseudouridines or pseudouridine analogs.

16. The method of claim 13 , wherein the mRNA is fully modified with N1-methylpseudouridine.

17. The method of claim 13 , wherein the mRNA is formulated in a lipid nanoparticle.

18. The method of claim 2 , wherein the RNA element has a 3 ′ end located 7 nucleotides upstream of the initiation codon.

19. The method of claim 8 , wherein the RNA element has a 3 ′ end located 7 nucleotides upstream of the initiation codon.

Assignments (2)
SECURITY INTEREST Recorded Nov 19, 2025
From: MODERNATX, INC.
To: ARES CAPITAL CORPORATION, AS AGENT
Reel/Frame 073634/0354 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 21, 2022
From: MOORE, MELISSA J.; KÖHRER, CAROLINE; JAIN, RUCHI; PRESNYAK, VLADIMIR
To: MODERNATX, INC.
Reel/Frame 061839/0252 →
Continuity (5)
Continuation 16614245
Provisional Application 62667824 · May 7, 2018
Provisional Application 62519800 · Jun 14, 2017
Provisional Application 62508318 · May 18, 2017
Related Publication 20230257738A1 · Aug 17, 2023
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