An lncRNA integrates a DNA-PK-mediated DNA damage response and vascular senescence
AssigneeThe Brigham and Women S Hospital, Inc.
InventorsMark W. Feinberg, Stefan Haemmig
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Abstract
Methods and compositions for use in treating subjects suffering from a disease associated with a malfunction in DNA repair response using compositions that comprise or encode SNHG12 long non-coding RNA.
Claims21
A method of treating a subject who has a disease associated with a malfunction in DNA repair response, the method comprising:
- administering to the subject a therapeutically effective dose of a pharmaceutical composition that increases expression of Small Nucleolar Host Gene-12 (SNHG12) long non-coding RNA in a cell of the subject in need thereof.
The method of claim 3, wherein the expression vector comprises an adeno-associated virus (AAV), adenovirus, lentivirus, or a DNA plasmid.
The method of claim 9, wherein the at least one chemical modification comprises a modification selected from phosphorothioate, boranophosphate, 4′-thio-ribose, locked nucleic acid, 2′-O-(2′-methoxyethyl), 2′-O-alkyl, 2′-O-alkyl-O-alkyl, 2′-O-methyl, 2′-fluoro, 2′-amino, or 2′-deoxy-2′-fluoro-b-D-arabinonucleic acid.
A pharmaceutical composition for use in treating a subject suffering from a disease associated with a malfunction in DNA repair response, comprising a nucleic acid molecule comprising (i) all or part of the SNHG12 long-coding RNA sequence, or (ii) a sequence encoding all or part of the SNHG12 long-coding RNA, optionally in an expression vector.
The pharmaceutical composition for the use of claim 14, wherein the expression vector comprises an adeno-associated virus (AAV), adenovirus, lentivirus, or a DNA plasmid.
The pharmaceutical composition for the use of claim 16, wherein the nucleic acid has at least 80% sequence identity with SEQ ID NO:
- 1 or 2 and is capable of increasing the expression of Small Nucleolar Host Gene-12 (SNHG12) long non-coding RNA.
20-21. (canceled)
Dependencies are inferred from the claim text.