tRNA derived small RNAs (tsRNAs) involved in cell viability

Patent metadata

Field	Value
Publication number	US-9428537-B2
Application number	US-201414214032-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Aug 30, 2016
Grant date	Aug 30, 2016

Abstract

The present invention features compositions and methods relating to tRNA-derived small RNAs (tsRNAs). Provided herein are oligonucleotide compositions that are complementary to tsRNAs, in particular leuCAGtsRNA, and methods of using the oligonucleotides for the regulation of respective tsRNA. Further provided are methods of inducing apoptosis through the inhibition of leuCAGtsRNA.

First claim

What is claimed is:

1. An oligonucleotide that is complementary to a tRNA-derived small RNA (tsRNA), wherein the oligonucleotide is selected from the group consisting of:

(a) tGTcAGgAgTggGaT;
(SEQ ID NO: 2)

and

(b) GGTGtcaggagtggGATT,
(SEQ ID NO: 11)

wherein uppercase letters represent locked nucleic acids and lowercase letters represent unmodified nucleic acids.

2. A pharmaceutical composition comprising the oligonucleotide of claim 1 , and a pharmaceutically acceptable carrier.

3. A method of inhibiting viability of a cell, the method comprising administering to the cell the oligonucleotide of claim 1 .

4. The method of claim 3 , wherein the inhibiting prevents cell proliferation, induces apoptosis, or induces cellular necrosis.

5. The method of claim 4 , wherein the inhibiting induces apoptosis.

6. A method of inhibiting viability of a cell, the method comprising inhibiting the function of leucine-CAG tsRNA, said method comprising administering to said cell an amount of the oligonucleotide of claim 1 sufficient to inhibit said viability of said cell.

7. The method of claim 6 , wherein the inhibiting viability of a cell prevents cell proliferation, induces apoptosis, or induces cellular necrosis.

8. The method of claim 7 , wherein the inhibiting viability of a cell induces apoptosis.

9. The oligonucleotide of claim 1 , wherein the oligonucleotide is tGTcAGgAgTggGaT (SEQ ID NO: 2).

10. The oligonucleotide of claim 1 , wherein the oligonucleotide is GGTGtcaggagtggGATT (SEQ ID NO: 11).

11. A pharmaceutical composition comprising the oligonucleotide of claim 9 , and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising the oligonucleotide of claim 10 , and a pharmaceutically acceptable carrier.

Assignees

• Univ Leland Stanford Junior

Inventors

• Kay Mark A
• Kim Hak Kyun
• Wang Shengchun

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C12N2310/3231

  having an additional ring, e.g. LNA, ENA · CPC title

• C07H21/02 Primary

  with ribosyl as saccharide radical · CPC title

• A61K31/606

  having amino groups · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title