Nuclease-mediated repeat expansion

A method for producing a modified cell with an increased number of copies of a repeat sequence at a target genomic locus, comprising:

• (a) providing a population of cells comprising a repeat expansion sequence comprising a plurality of copies of the repeat sequence at the target genomic locus;
• (b) introducing into the population of cells a nuclease agent or a nucleic acid encoding the nuclease agent,
• wherein the nuclease agent is a zinc finger nuclease (ZFN), a Transcription Activator-Like Effector Nuclease (TALEN), or a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated (Cas) protein and a guide RNA, and
• wherein the nuclease agent makes a double-strand break or a single-strand break at a nuclease target site within about 25 nucleotides of the 5′ end or the 3′ end of the repeat expansion sequence to produce a population of modified cells;
• and
• (c) quantifying the number of copies of the repeat sequence in the population of modified cells and selecting a modified cell in which the number of copies of the repeat sequence has been increased.