Down's syndrome is a common genetic disorder and is caused by the presence of three copies of chromosome 21. The authors of this study attempted to correct the gene over-dose across a whole chromosome by manipulating a single gene. An inducible version of XIST (the X-inactivation gene) was inserted into one copy of chromosome 21 in Down's syndrome pluripotent stem cells. The edited chromosome was enriched in repressive histone marks and chromosome-wide transcriptional silencing was achieved 5 days after XIST induction. The reversal of deficits in cell proliferation and neurogenesis that were observed suggests that this approach could eventually lead to gene therapies that reduce the symptoms of Down's syndrome.