Scan-based fusion proteins for modulating gene expression and methods of use

The invention provides fusion protein comprising a SCAN domain bearing member of a zinc finger-containing protein, a fragment or variant thereof and a catalytically inactive RNA- guided endonuclease or a DNA adenine methyltransferase. Preferably, the fusion protein is for use in the treatment and/or prevention of cancer, neurodegenerative disease, neurodevelopmental disease, aging and aging-related disease.