Grant: Project Grant

Over 40 diseases, including incurable and fatal neurodegenerative diseases such as ALS, are caused by the expansion of repetitive sequences in the genome. Beyond a certain size, these expansions cause problems in the cells and the body, leading to disease. These diseases are engrained in the patients' DNA, where, for instance, instead of having 10 repeats of the genetic letters "CAG", a patient can have over 20 repeats of this same "CAG". Therefore, as opposed to infectious diseases caused by a pathogen invading the body, it is currently not possible to get rid of the source of the disease for the individuals who are suffering from it. Moreover, the type of mutations at the origin of these diseases is even more difficult to target than other single base mutations (where a single "letter" of the genetic code is modified) because the modern genetic tools that can provide hope for many hereditary diseases typically recognize ~20 bases ("letters") of sequence, which does not allow to distinguish the number of repeats between a healthy individual and someone with the disease This project aims at developing an artificially intelligent (AI) algorithm, realized as a computer program that will generate a molecular tool capable of making such a distinction. This program will design an RNA molecule that will be switched-ON only in presence of repeats exceeding the "healthy number", when switched-ON, this RNA molecule will act as a molecular scissor that will cleave the product of the disease-causing gene, leaving only the healthy version intact. This program will use this common feature from these genetic diseases as a means to automatically design specific gene inactivating tools for therapy.