# US 2023/0054941 A1 · Inhibition of dennd5b expression for treating hepatic steatosis

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- Number: US 2023/0054941 A1
- Document ID: US20230054941A1
- Status: Published application
- Kind: A1
- Application number: 17/792,388
- Filed: 2021-01-13
- Published: 2023-02-23
- Earliest claimed: 2020-01-13
- Assignees: University of Kentucky Research Foundation
- Applicants: University of Kentucky Research Foundation
- Inventors: Scott Gordon
- Web page: https://patentgrep.com/patent/US20230054941A1

## CPC

- C07K 14/82: Translation products from oncogenes
- 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)}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- C07K 14/4705: {stimulating, promoting or activating activity}
- C12N 9/222: {Clustered regularly interspaced short palindromic repeats [CRISPR]-associated [CAS] enzymes}
- 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 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2310/3231: having an additional ring, e.g. LNA, ENA
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods of treating hepatic steatosis involve administering to a subject a DENND5B inhibitor, thereby reducing the expression of and/or activity of DENND5B in liver of the subject. The DENND5B inhibitor can include antisense oligonucleotide (ASO), CRISPR interference (CRISPRi), miRNA, siRNA, locked nucleic acid (LNA) nucleotides, or a combination thereof.

## Claims

### Claim 1

A method of treating hepatic steatosis, comprising:
identifying a subject having or at risk of developing hepatic steatosis, and
administering to the subject a DENND5B inhibitor, thereby reducing the expression of and/or activity of DENND5B in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the DENND5B inhibitor comprise antisense oligonucleotide (ASO), CRISPR interference (CRISPRi), miRNA, siRNA, locked nucleic acid (LNA) nucleotides, or a combination thereof.

### Claim 3 (depends on 2)

The method of claim 2, wherein the inhibitor comprises a guide antisense strand consisting of about 10 to about 30 nucleotides.

### Claim 4 (depends on 3)

The method of claim 3, wherein the guide antisense strand consists of about 10 to about 30 nucleotides consecutive nucleotides of SEQ ID NO: 1, or a complement thereof.

### Claim 5 (depends on 3)

The method of claim 3, wherein the guide antisense strand consists of about 10 to about 30 nucleotides consecutive nucleotides within the first 2216 nucleotides of SEQ ID NO: 1, or a complement thereof.

### Claim 6 (depends on 1)

The method of claim 1, and further comprising targeting the reducing the expression of and/or activity of DENND5B to the liver using a targeting moiety.

### Claim 7 (depends on 6)

The method of claim 6, wherein the DENND5B inhibitor reduces the expression of DENND5B in the liver.

### Claim 8 (depends on 1)

The method of claim 1, wherein the DENND5B inhibitor employs a nucleotide molecule targeting a protein coding region of DENND5B gene.

### Claim 9 (depends on 1)

The method of claim 1, wherein the DENND5B inhibitor employs a nucleotide molecule targeting a non-coding region of DENND5B gene.

### Claim 10 (depends on 9)

The method of claim 9, wherein the nucleotide molecule targets promoter of DENND5B gene.

### Claim 11 (depends on 9)

The method of claim 9, wherein the nucleotide molecule targets promoter of DENND5B gene 3′ untranscribed regions (UTRs) of DENND5B gene.

### Claim 12 (depends on 1)

The method of claim 1, wherein the subject is identified as having a risk of developing hepatic steatosis when the subject has diet-induced fatty liver disease; the subject has been identified as being at risk of developing diet-induced fatty liver disease; the subject has non-alcohol-induced fatty liver disease; the subject has been identified as being at risk of developing non-alcohol-induced fatty liver disease; the subject is obese as determined by BMI and/or abdominal circumference; the subject has type II diabetes; the subject has alcohol-induced fatty liver disease; and/or the subject has been identified as being at risk of developing alcohol-induced fatty liver disease.