RNA products and uses thereof
AssigneeIfom - Fondazione Istituto Firc Di Oncologia Molecolare
InventorsFabrizio d'Adda di Fagagna, Sofia Francia, Flavia Michelini, Francesca Rossiello
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Abstract
The present invention relates to small RNAs, inhibitors thereof, inhibitors of enzymes producing thereof, and their use to modulate the response of a cell to a DNA damaging event. The invention concerns also a method to detect the presence or quantify DNA damage.
Claims17
A method for the treatment of a condition induced by a sequence specific damaged genomic locus, wherein the damage occurs at telomeres and/or is caused by a sequence-specific DNA endonuclease, the method comprising:
- administering an inhibitor of small RNAs (DDRNAs), wherein the DDRNAs are generated in cis by processing an RNA transcript with DICER and/or DROSHA;
- wherein said RNA transcript was synthesized using the sequence specific damaged genomic locus as a template for transcription;
- wherein the DDRNAs comprise a sequence of the sequence specific damaged genomic locus;
- and
- wherein the inhibitor is at least one exogenous sequence specific inhibitory oligonucleotide.
A method for the treatment of a condition induced by a sequence specific damaged genomic locus, the method comprising:
- administering an inhibitor of small RNAs (DDRNAs), wherein the DDRNAs are generated in cis by processing an RNA transcript of the damaged genomic locus with DICER and/or DROSHA;
- wherein said RNA transcript was synthesized using the sequence specific damaged genomic locus as a template for transcription;
- wherein the DDRNAs comprise the sequence of the sequence specific damaged genomic locus;
- wherein the inhibitor is at least one exogenous sequence specific inhibitory oligonucleotide;
- and
- wherein the condition is selected from the group consisting of senescence induced by:
- persistent DNA damage response activation at damaged telomeres;
- and oncogene-induced senescence.
A method for the treatment of a condition induced by a sequence specific damaged genomic locus wherein the damage occurs at telomeres or is caused by a sequence-specific DNA endonuclease, the method comprising:
- administering an inhibitor of small RNAs (DDRNAs), wherein the DDRNAs are generated in cis by processing an RNA transcript of the damaged genomic locus with DICER and/or DROSHA;
- wherein said RNA transcript was synthesized using the sequence specific damaged genomic locus as a template for transcription;
- wherein the DDRNAs comprise the sequence of the sequence specific damaged genomic locus;
- wherein the inhibitor is at least one exogenous sequence specific locked nucleic acid, siRNA, 2′-O-methyl-modified oligonucleotide, or phosphorothioate modified oligonucleotide;
- and
- wherein the condition is selected from the group consisting of senescence induced by:
- persistent DNA damage response activation at damaged telomeres;
- and oncogene-induced senescence.
Dependencies are inferred from the claim text.