The present invention is in the field of genetic editing tools and methods of genetic engineering. It relates to the engineering of rare-cutting endonucleases designed to contract highly repetitive motives in chromosomes, which are at the origin of certain genetic diseases, in particular the so-called “triplet repeat diseases”, such as the Huntington disease. The invention encompasses the method for contracting the repetitive motives, the rare-cutting endonucleases for use to contract repetitive motives in a gene subjected to repeat disorder, the polynucleotides and vectors encoding thereof as well as the resulting pharmaceutical compositions.
