The genesis of the siDNA concept

The genesis of the siDNA concept
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The genesis of the siDNA concept

The genesis of the siDNA (signal interfering DNA) concept and its successful demonstration are examples of fruitful translational research where clinicians and scientists shared their viewpoints on clinical bottlenecks and combined their imaginations, intelligences and efforts in moving forward innovative therapeutic solutions against treatment-resistant cancer.

The story began in June 2001, when Jean-Marc Cosset, head of the Department of radio-oncology at the Institut Curie talked about the problem of radioresistance in the treatment of head-and-neck cancer to his colleague, Marie Dutreix, a radiobiologist and specialist of genomic instability and DNA repair. Marie Dutreix thought that such radio-resistance arose from high DNA repair capacity of tumor cells to escape radiation caused DNA damages, in particular, the most lethal double strand breaks (DSBs).

In July 2001, Marie Dutreix discussed this issue and her viewpoint with Jian Sheng Sun, a physical chemist and specialist in nucleic acids and related biotechnologies. They agreed to brainstorm on this new approach 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 mimicof 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 neutralization of tumor cells’ DNA repair capacity could open a therapeutic window for sensitizing radiotherapy. In October 2001, the Institut Curie allocated a four-year grant (2002-2005) to this innovative project. The project involved several research teams (Dr. Dutreix, project manager; Dr. Larue; Prof. Debatisse; Dr. Robine; …) and medical teams (Prof. Cosset; Dr. Sastre; …) at the Institut Curie, and Prof. Sun at the Muséum National d’Histoire Naturelle (MNHN).

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 permit the maturation of siDNA technology, and the inception of DNA Therapeutics Inc. in May 2006. The founders are grateful to the people who have contributed to this project.

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