IP Library › Granted Patent US 12,448,620
Granted Patent B2
US 12,448,620 · App. 17/817,874 · Granted Oct 21, 2025

RNA-editing oligonucleotides and uses thereof

Inventors: Andrew W. Fraley (Arlington, MA); Steven Robinette (Fremont, NH); Nessan Bermingham (Boston, MA); Mallikarjuna Reddy Putta (Lexington, MA)
Assignee: KORRO BIO, INC.
C12N15/11C12N2310/315C12N2310/321C12N2310/351
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Quick Facts
Patent No.
US 12,448,620
App. No.
17/817,874
Granted
Oct 21, 2025
Kind
B2
Abstract

The present disclosure features useful compositions and methods to treat disorders for which deamination of an adenosine in an mRNA produces a therapeutic result.

Claims (37)

1. An oligonucleotide comprising the structure:

[A m ]-X 1 -X 2 -X 3 -[B n ]

wherein each of A and B is a nucleotide, and at least 20% of the nucleotides of [Am] and [Bn] combined are 2′-O-methyl-nucleotides;

m and n are each, independently, an integer from 1 to 50;

X 1 , X 2 , and X 3 are each, independently, a nucleotide, wherein X 1 or X 3 has the structure of Formula II:

wherein N 1 is a nucleobase;

R 8 is hydrogen; and

R 9 is hydrogen.

2. The oligonucleotide of claim 1 , wherein at least 80% of the nucleotides of [A m ] and/or [B n ] include a nucleobase, a sugar, and an internucleoside linkage.

3. The oligonucleotide of claim 1 , wherein X 1 has the structure of Formula II.

4. The oligonucleotide of claim 1 , wherein X 3 has the structure of Formula II.

5. The oligonucleotide of claim 1 , wherein X 2 has the structure of any one of Formula I-IV:

wherein N 1 is hydrogen or a nucleobase;

R 6 is hydrogen, hydroxy, or halogen;

R 7 is hydrogen, hydroxy, halogen, or C 1 -C 6 alkoxy;

R 8 is hydrogen or halogen;

R 9 is hydrogen or hydroxy, halogen, or C 1 -C 6 alkoxy;

R 10 is hydrogen or halogen; and

R 11 is hydrogen or hydroxy, halogen, or C 1 -C 6 alkoxy.

6. The oligonucleotide of claim 1 , wherein at least 90% of the nucleotides of [A m ] and [B n ] include a nucleobase, a sugar, and an internucleoside linkage.

7. The oligonucleotide of claim 1 , wherein each of X 1 , X 2 , and X 3 that does not have the structure of Formula II is, independently, a ribonucleotide, a 2′-O—C 1 -C 6 alkyl-nucleotide, a 2′-amino-nucleotide, an arabinonucleic acid-nucleotide, a bicyclic-nucleotide, a 2′-F-nucleotide, 2′-O-methoxyethyl-nucleotide, a constrained ethyl-nucleotide, an LNA-nucleotide, or a DNA-nucleotide.

8. The oligonucleotide of claim 1 , wherein X 1 includes a uracil or thymine nucleobase and X 3 includes a hypoxanthine nucleobase.

9. The oligonucleotide of claim 1 , wherein X 2 includes a cytosine nucleobase.

10. The oligonucleotide of claim 1 , wherein each of X 1 , X 2 , and X 3 that does not have the structure of Formula II is not a 2′-O-methyl-nucleotide.

11. The oligonucleotide of claim 1 , wherein [A m ] and/or [B n ] comprises at least one 2′-F-nucleotide, at least one 2′-O-methoxyethyl-nucleotide, at least one cEt-nucleotide, at least one LNA-nucleotide, and/or at least one DNA-nucleotide.

12. The oligonucleotide of claim 1 , wherein [A m ] and/or [B n ] comprises at least one phosphorothioate linkage.

13. The oligonucleotide of claim 1 , wherein [A m ] and/or [B n ] comprises at least four terminal phosphorothioate linkages.

14. The oligonucleotide of claim 1 , wherein at least 30% of the nucleotides of [A m ] and [B n ] combined are 2′-O-methyl-nucleotides.

15. The oligonucleotide of claim 1 , wherein A and B combined consist of 27 to 71 nucleotides.

16. The oligonucleotide of claim 1 , wherein X 1 includes a uracil or thymine nucleobase and X 3 includes a hypoxanthine nucleobase; X 2 includes a cytosine nucleobase; and each of X 1 and X 3 is, independently, a 2′-O—C 1 -C 6 alkyl-nucleotide, a 2′-F-nucleotide, an arabinonucleic acid-nucleotide, or a DNA-nucleotide.

17. The oligonucleotide of claim 16 , wherein at least 95% of the nucleotides of [A m ] and [B n ] include a nucleobase, a sugar, and an internucleoside linkage; each of [A m ] and [B n ] comprises at least one phosphorothioate linkage; each of [A m ] and [B n ] comprises at least one 2′-O-methyl-nucleotide, at least one 2′-F-nucleotide, at least one 2′-O-methoxyethyl-nucleotide, at least one cEt-nucleotide, at least one LNA-nucleotide, and/or at least one DNA-nucleotide; and A and B combined consist of 27 to 71 nucleotides.

18. A complex comprising:

the oligonucleotide of claim 1 ; and an mRNA,

wherein the oligonucleotide and mRNA are hybridized to each other and the complex

comprises a first mismatch at an adenosine of the mRNA.

19. A method for deamination of an adenosine in an mRNA, the method comprising contacting a cell with the oligonucleotide of claim 1 .

20. A method of treating a disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of the oligonucleotide of claim 1 .

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 28, 2024
From: FRALEY, ANDREW W.; BERMINGHAM, NESSAN; PUTTA, MALLIKARJUNA REDDY
To: KORRO BIO, INC.
Reel/Frame 067543/0133 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 28, 2024
From: ROBINETTE, STEVEN
To: ATLAS VENTURE LIFE SCIENCE ADVISORS, LLC
Reel/Frame 067543/0271 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 28, 2024
From: ATLAS VENTURE LIFE SCIENCE ADVISORS, LLC
To: KORRO BIO, INC.
Reel/Frame 067543/0343 →
Continuity (5)
Continuation 16749601 · Jan 22, 2020
Provisional Application 62900017 · Sep 13, 2019
Provisional Application 62822586 · Mar 22, 2019
Provisional Application 62795348 · Jan 22, 2019
Related Publication 20230104978A1 · Apr 6, 2023
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