# US 2020/0399303 A1 · Rna-editing oligonucleotides and uses thereof

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- Number: US 2020/0399303 A1
- Document ID: US20200399303A1
- Status: Published application
- Kind: A1
- Application number: 16/749,500
- Filed: 2020-01-22
- Published: 2020-12-24
- Earliest claimed: 2019-01-22
- Assignees: Korro Bio, Inc.
- Applicants: Korro Bio, Inc.
- Inventors: Andrew W. FRALEY; Steven ROBINETTE; Nessan BERMINGHAM; Mallikarjuna Reddy PUTTA
- Web page: https://patentgrep.com/patent/US20200399303A1

## CPC

- C07H 19/16: Purine radicals
- C07H 19/06: Pyrimidine radicals
- C07H 21/00: Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C12N 15/11: DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 2310/11: Antisense
- C12N 2310/315: Phosphorothioates
- C12N 2310/3181: Peptide nucleic acid, PNA
- C12N 2310/3183: Diol linkers, e.g. glycols or propanediols
- C12N 2320/50: Methods for regulating/modulating their activity
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## 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, e.g., in a subject in need thereof.

## Claims

### Claim 1

An oligonucleotide comprising the structure:
[Am]-X1-X2-X3—[Bn]
wherein each of A and B is a nucleotide;
m and n are each, independently, an integer from 1 to 50;
X1, X2, and X3 are each, independently, a nucleotide, wherein at least one of X1, X2, or X3 has the structure of any one of Formula I-VI:
wherein N1 is hydrogen or a nucleobase;
R12 is hydrogen, hydroxy, fluoro, halogen, C1-C6 alkyl, C1-C6 heteroalkyl, or C1-C6 alkoxy;
R13 is hydrogen or C1-C6 alkyl,
wherein at least one of X1, X2, or X3 has the structure of any one of Formula I-IV.

### Claim 2 (depends on 1)

The oligonucleotide of claim 1, wherein at least 80% of the nucleotides of [Am] and/or [Bn] include a nucleobase, a sugar, and an internucleoside linkage.

### Claim 3 (depends on 1)

The oligonucleotide of claim 1, wherein R12 is hydrogen, halogen, C1-C6 alkyl, or C1-C6 heteroalkyl.

### Claim 4 (depends on 1)

The oligonucleotide of claim 1, wherein the halogen is fluoro.

### Claim 5 (depends on 1)

The oligonucleotide of claim 1, wherein R12 is hydrogen or C1-C6 alkyl;

### Claim 6 (depends on 1)

The oligonucleotide of claim 1, wherein R12 is hydrogen.

### Claim 7 (depends on 1)

The oligonucleotide of claim 1, wherein at least one of X1, X2, and X3 has the structure of Formula I, and N1 is a nucleobase.

### Claim at position 8

8-9. (canceled)

### Claim 10 (depends on 1)

The oligonucleotide of claim 1, wherein at least one of X1, X2, and X3 has the structure of Formula II, and N1 is a nucleobase.

### Claim at position 10

11-12. (canceled)

### Claim 13 (depends on 1)

The oligonucleotide of claim 1, wherein at least one of X1, X2, and X3 has the structure of Formula IV, and N1 is a nucleobase.

### Claim at position 12

14-15. (canceled)

### Claim 16 (depends on 1)

The oligonucleotide of claim 1, wherein at least one of X1, X2, and X3 has the structure of Formula III, and N1 is a nucleobase.

### Claim at position 14

17-52. (canceled)

### Claim 53 (depends on 1)

The oligonucleotide of claim 1, wherein at least 20% of the nucleotides of [Am] and [Bn] combined are 2′-O-methyl-nucleotides.

### Claim at position 16

54-56. (canceled)

### Claim 57 (depends on 1)

The oligonucleotide of claim 1, wherein A and B combined consist of 18 to 80 nucleotides.

### Claim at position 18

58-59. (canceled)

### Claim 60 (depends on 1)

The oligonucleotide of claim 1, wherein m and n are each, independently, an integer from 5 to 40; at least one of X1, X2, and X3 has the structure of Formula I, Formula II, Formula III, or Formula IV, wherein N1 is a nucleobase and each of X1, X2, and X3 that does not have the structure of Formula I, Formula II, Formula III, or Formula IV is a ribonucleotide; [Am] and [Bn] each include at least five terminal 2′-O-methyl-nucleotides and at least four terminal phosphorothioate linkages; and at least 20% of the nucleotides of [Am] and [Bn] combined are 2′-O-methyl-nucleotides.

### Claim 61 (depends on 1)

The oligonucleotide of claim 1, wherein the oligonucleotide further comprises one or more adenosine deaminase acting on RNA (ADAR)-recruiting domains.

### Claim 62 (depends on 1)

A conjugate comprising an oligonucleotide of claim 1 conjugated to a targeting moiety.

### Claim 63

(canceled)

### Claim 64 (depends on 1)

A complex comprising:
an oligonucleotide of claim 1; and
an mRNA,
wherein the oligonucleotide or conjugate and mRNA are hybridized to each other and the complex comprises a first mismatch at an adenosine of the mRNA.

### Claim at position 24

65-72. (canceled)

### Claim 73 (depends on 1)

A method of producing a complex, the method comprising contacting a cell with an oligonucleotide of claim 1.

### Claim 74 (depends on 1)

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

### Claim 75 (depends on 1)

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

### Claim 76

(canceled)