Disclosed herein are methods and compositions for treating Huntingtons Disease. In particular, provided herein are methods and compositions for modifying (e.g., modulating expression of) an HD Htt allele so as to treat Huntington Disease. Also provided are methods and compositions for generating animal models of Huntingtons Disease. Thus, in one aspect, engineered (non-naturally occurring) DNA binding domains (e.g., zinc finger proteins, TAL effector (TALE) proteins or CRISPR/dCas-TF) that modulate expression of a HD allele (e.g., Htt) are provided.
