DNA Therapeutics: Particular features

DNA Therapeutics: Particular features In cell culture, it was observed in the unstressed, normal cells treated by Dbait molecules that: i Comet test which measures the extent of DNA damages was negative. These data indicate the absence of DNA damages induced by Dbait molecules. In animals, the treatment of Dbait in healthy tissue did not show any sign of toxicity at the therapeutically active dose to tumors. This suggests again that the short term DNA repair inhibition is not lethal to normal cells and tissues. Cancer cells are more sensitive to the inhibition of DNA repair than normal cells, because: – their rapid growth has less time to carry out DNA repair;– their replication under stress increases endogenous DNA damages, including DSBs;– their impaired cell cycle control leads to mitotic catastrophe if one DSB remained;– their greater genetic instability than normal cells;– their reliance on fewer DNA repair pathways enhances the effect of disrupting a DNA repair pathway. After the emergence of molecular therapies led by monoclonal antibodies, and kinase inhibitors that act on cell proliferation, differentiation and apoptosis, DNA repair pathway is becoming a compelling therapeutic target in cancer therapy. Targeting to DNA repair pathways is an ubiquitous approach applicable to all types of tumors because it acts on the well conserved mechanisms of DNA maintenance in every living cells. This clearly is addressed by DNA Therapeutics’ siDNA technology and its derived therapeutics. Dbait is a first-in-class drug candidate with a new mechanism of action to block DSB repair and to overcome radio - and chemoresistance of tumors. Therefore, it considerably adds value to the existing therapies, not only radio - and chemotherapies, but also other emerging molecular therapies. Dbait molecule is a mimic of DSB. It does not act as a classic inhibitor but as a DSB signaling jammer that disorganizes all DSB repair systems. This prevents the escape of tumor cells to the treatment by bypassing to an alternative pathway when the targeted pathway is blocked;Unlike monoclonal antibody, kinase inhibitor, aptamer and decoy oligonucleotides, Dbait does not target a specific protein per se;Unlike antisense, siRNA and miRNA oligonucleotides, Dbait does not inhibit any mRNA expression;Due to its mode of action through the recognition of a molecular structure, DSB, the sequence of Dbait does not matter.

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