Abstract
Nonsense mutations lead to the absence of expression of the mutant gene and are responsible for approximately 10% of cases of genetic diseases. Very few recorded molecules are capable of inducing the re-expression of a gene carrying a nonsense mutation by what is called readthrough. It is by screening extracts from plants, mushrooms and marine microorganisms that we selected the extract of Paralepista flaccida as having very strong readthrough activity. This rather common mushroom in France seems to be distinguished from mushrooms that are closed related but which do not have this readthrough activity. We then identified the active principle responsible for the readthrough activity. This is 2,6-diaminopurine (DAP) which has never been reported to correct nonsense mutations. This molecule represents therapeutic hope for all patients suffering from a genetic disease caused by a nonsense mutation and who are without treatment today. This type of study illustrate the interest in searching in nature for future drugs: only 20,000 extracts were tested to reveal this species, when other research groups had to test more than 800,000 molecules to select a single molecule with low activity.