DNA Therapeutics: History The genesis of the signal interfering

DNA Therapeutics: History The genesis of the signal interfering DNA (siDNA) concept is an example of fruitful exchange between physicians and scientists, sharing clinical bottleneck and combining their imaginations and efforts to develop new solution against treatment-resistant cancer. The story began in June 2001, when Prof. Jean-Marc Cosset, head of the Department of oncology radiotherapy at the Institut Curie talked about the radioresistance in head-and-neck cancer to his colleague, Dr. Marie Dutreix, a radiobiologist and an expert of genomic instability and DNA repair. Dr. Dutreix thought that such radio-resistance may arise from enhanced DNA repair capacity of tumor cells to get rid of DNA damages inflicted by radiation, in particular, the most lethal double strand breaks (DSBs). Later on, Dr. Dutreix shared this problem and her thought with Prof. Jian Sheng Sun, an expert in nucleic acids and related biotechnologies. They agreed to brainstorm on this topic during the summer vacation and to submit a translational research project to the Scientific Advisory Board of the Institut Curie. The project entitled “Genomic instability and radioresistance in tumors” proposed to develop a substrate mimicking DSBs (“DSB bait” molecules, “Dbait” for short) and to introduce Dbait in cells in order to interfere with DNA damage sensing, signaling and repair activities They postulated that the transient impairment of tumor cells’ DNA repair capacity could open a therapeutic window for sensitizing radiotherapy. The Institut Curie allocated a 4 year grant (2002-2005) to this project which involved several research and medical teams at the Institut Curie, and Prof. Sun, then, at the Muséum National d’Histoire Naturelle. Soon after the first in vivo proof of concept, in January 2004, Prof. Sun and Dr. Dutreix decided to further validate the concept in other tumor models and to strengthen intellectual property in order to transform this translational research project into a start-up project led by Prof. Sun. Since then, the project has received many scientific and financial supports which helped the maturation of siDNA technology, and the inception of DNA Therapeutics in June 2006.


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