METHOD FOR RE-EXPRESSION OF DIFFERENT HYPERMETHYLATED GENES INVOLVED IN FIBROSIS, LIKE HYPERMETHYLATED RASAL,1 AND USE THEREOF IN TREATMENT OF FIBROSIS AS WELL AS KIT OF PARTS FOR RE-EXPRESSION OF HYPERMETHYLATED GENES INCLUDING RASAL1 IN A SUBJECT

摘要

The present invention relates to a method for re-expression of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO based on an inactivated CRISPR-based system and a DNA dioxygenase as well as a gRNA guiding said construct to the RASAL1, LRFN2, and KLOTHO gene for demethylation of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO, in particular, hypermethylated RASAL1, LRFN2, and KLOTHO promoter, thus, allowing re-expression of RASAL1, LRFN2, and KLOTHO for the treatment of fibrosis, cancer or neuronal disorders in a subject. Further, the present invention relates to a kit of parts for allowing re-expression of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO in a subject comprising nucleic acid encoding the gRNA as defined above as well as a fusion protein of an inactive CRISPR based system and a DNA dioxygenase. Finally, the present invention provides a vector or vector system composed of at least two vectors, the vector or vector system comprises the nucleic acids encoding the gRNA as well as the fusion protein in a single vector or in two vectors. Further, nucleic acid constructs are provided comprising the nucleic acid encoding the gRNA as well as the fusion protein.