# US 2018/0023080 A1 · Long Non-Coding RNA For The Treatment Of Endothelial Dysfunction

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- Number: US 2018/0023080 A1
- Document ID: US20180023080A1
- Status: Published application
- Kind: A1
- Application number: 15/548,329
- Filed: 2016-02-03
- Published: 2018-01-25
- Earliest claimed: 2015-02-03
- Assignees: Johann Wolfgang Goethe-Universität Frankfurt am Main
- Applicants: Johann Wolfgang Goethe-Universität Frankfurt am Main
- Inventors: Stefanie DIMMELER; Reinier BOON; Nicolas JAÉ; Katharina MICHALIK
- Web page: https://patentgrep.com/patent/US20180023080A1

## CPC

- 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)}
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 35/00: Antineoplastic agents
- C12N 2310/11: Antisense
- C12N 2310/113: targeting other non-coding nucleic acids, e.g. antagomirs
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/341: Gapmers, i.e. of the type ===---===
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention associates multiplelong non-coding RNA (lncRNA) with key functions of endothelial cells. The lncRNA of the present invention are therefore useful as novel drug targets for the manufacturing of medicines for the treatment of cardiovascular diseases or pathological angiogenesis in context of proliferative diseases such as cancer. Modulation of the function or expression of the lncRNA of invention can induce or repress angiogenesis and vessel growth or repair in endothelial cells. Provided are further methods for the modulation of endothelial cell functions in vitro, for example, in the context of tissue engineering.

## Claims

### Claim 1

A method of treating a disease associated with endothelial cell dysfunction in a subject, comprising the step of administering to the subject a composition that includes a compound that is an agonist or an antagonist of a long non-coding RNA (lncRNA) selected from the group consisting of lnc-KPNA2, lnc-SERTAD2, lnc-Hyp_up_1, lnc-Hyp_down_1, lnc-Meg3, lnc-RNF151, lnc-Hyp_up_3, lnc-Hyp_up_5, and lnc-GDF7.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject administered the composition has a disease associated with endothelial cell dysfunction that is pathological angiogenesis, and wherein the composition is
an antagonist of a long non-coding RNA (lncRNA) selected from the group consisting of lnc-KPNA2, lnc-SERTAD2, and lnc-Hyp_up_1, or an agonist of an lncRNA selected from lnc-Hyp_down_1 and lnc-Meg3.

### Claim 3 (depends on 2)

The method of claim 2, wherein the pathologic angiogenesis in the subject administered the composition occurs in connection with a proliferative disorder and wherein the proliferative disorder is a cancer.

### Claim 4 (depends on 1)

The method of claim 1, wherein the subject administered the composition has a disease associated with endothelial cell dysfunction that is a cardiovascular disease, and wherein the composition is
an agonist of a long non-coding RNA (lncRNA) selected from the group consisting of lnc-KPNA2, lnc-SERTAD2, and lnc-Hyp_up_1, or an antagonist of an lncRNA selected from lnc-Hyp_down_1 and lnc-Meg3.

### Claim 5 (depends on 4)

The method of claim 4, wherein the cardiovascular disease in the subject administered the composition is a disease associated with a pathological repressed endothelial cell repair, cell growth and/or cell division or is a disease treatable by improving endothelial cell repair, cell growth and/or cell division.

### Claim 6 (depends on 1)

The method of of claim 1, wherein an lncRNA agonist is selected from the group of an lncRNA molecule, or a homolog thereof or an lncRNA expression construct, or a molecule that when contacted with a cell induces or increases the expression and or function of the lncRNA; and/or wherein an antagonist of a lncRNA is selected from an antagonistic peptide, an antagonistic small molecule, or an inhibitory nucleic acid, an antisense oligonucleotide, a miRNA, siRNA, dsRNA, LNA, GapmeR, or a molecule that represses the expression and/or function of a lncRNA.

### Claim 7

An in-vitro or ex-vivo method for modulating endothelial cell function, comprising the step of contacting an endothelial cell with an agonist or antagonist of a lncRNA selected from the group consisting of lnc-KPNA2, lnc-SERTAD2, lnc-Hyp_up_1, lnc-Hyp_down_1 and lnc-Meg3.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the endothelial cell function is a function selected from endothelial cell repair, endothelial cell growth and/or endothelial cell division.

### Claim 9

An in-vitro or ex-vivo method for the generation of vascular tissue material, comprising the step of contacting an endothelial cell with an agonist of a lncRNA, wherein the lncRNA is selected from the group consisting of lnc-KPNA2, lnc-SERTAD2, and lnc-Hyp_up_1, or an antagonist of a lncRNA selected from lnc-Hyp_down_1 and lnc-Meg3.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the vascular tissue material is a blood vessel.

### Claim 11 (depends on 9)

The method according to any of claim 9, wherein an lncRNA agonist is selected from the group of an lnc-RNA molecule, a chemically modified lnc-RNA molecule, or an lncRNA expression construct, or a molecule that when contacted with a cell induces or increases the expression and or function of the lncRNA.

### Claim 12 (depends on 9)

The method according to any one of claim 9, wherein an antagonist of a lncRNA is selected from an inhibitory nucleic acid, such as a miRNA, siRNA, dsRNA, LNA, GapmeR, or a molecule that represses the expression and/or function of a lncRNA.

### Claim 13

A pharmaceutical composition comprising an agonist or an antagonist of a long non-coding RNA (lncRNA) selected from the group consisting of lnc-KPNA2, lnc-SERTAD2, lnc-Hyp_up_1, lnc-Hyp_down_1, lnc-Meg3, lnc-RNF151, lnc-Hyp_up_3, lnc-Hyp_up_5 and lnc-GDF7.

### Claim 14

A method of treating a disease associated with endothelial cell dysfunction in a subject, comprising the step of administering to the subject a composition that includes a compound that is an agonist or an antagonist of a long non-coding RNA (lncRNA) selected from the group consisting of lnc-KPNA2, lnc-SERTAD2, lnc-Hyp_up_1, lnc-Hyp_down_1, lnc-Meg3, lnc-RNF151, lnc-Hyp_up_3, lnc-Hyp_up_5, and lnc-GDF7.

### Claim 15

A method of modulating endothelial cell function, comprising the step of contacting an endothelial cell with an agonist or antagonist of a long non-coding RNA (lncRNA) selected from the group consisting of lnc-KPNA2, lnc-SERTAD2, lnc-Hyp_up_1, lnc-Hyp_down_1, lnc-Meg3, lnc-RNF151, lnc-Hyp_up_3, lnc-Hyp_up_5 and lnc-GDF7.

### Claim 16 (depends on 3)

The method of claim 3, wherein the cancer is selected from the group consisting of liver cancer, lung cancer, breast cancer, colorectal cancer, stomach cancer and melanoma.

### Claim 17 (depends on 16)

The method of claim 16, wherein the cancer is a solid cancer.

### Claim 18 (depends on 17)

The method of claim 17, wherein the solid cancer is a metastatic solid cancer.

### Claim 19 (depends on 13)

The pharmaceutical composition of claim 13, further including an acceptable carrier and/or excipient.
