Dbait and uses thereof
AssigneesInstitut Curie, Centre National de la Recherche Scientifique (CNRS), Museum National D'Histoire Naturelle, Institut National De La Sante Et De La Recherche Medicale (Inserm)
InventorsMarie Dutreix, Jian-Sheng Sun
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Abstract
The invention relates to compositions and methods for interfering with the DNA repair of double strand breaks (DSBs). The invention discloses novel double-stranded nucleic acid molecules. that act as baits and hijack the holocomplex of enzymes responsible of DNA DSB sensing, signaling and/or repair pathways, in particular the non homologous end joining (NHEJ) pathway of DSB repair. The invention discloses the use of these molecules as adjuvant compositions to be used in association with a DNA breaking treatment, particularly radiotherapy or chemotherapy, in combination with a pharmaceutically acceptable carrier, in an efficient amount to be introduced in the tumor cell nuclei in order to neutralize transiently their DNA repair capacity and trigger their death.
Claims23
A nucleic acid molecule, wherein said molecule comprises a double stranded portion with the sequence of SEQ ID NO:5, has at least one free end, and wherein said molecule is substrate for binding by at least a Ku protein involved in the Non-Homologous End-Joining (NHEJ) pathway of double strand breaks (DSB) repair.
A molecule selected from Dbait32Hb (SEQ ID NO:5), and Dbait32Hc-5′5′ (SEQ ID NO:5).
Dependencies are inferred from the claim text.