A modified version of CRISPR-Cas9 has enabled, for the first time, the efficient integration of a large transgene capable of inactivating entire chromosomes into one of the three copies of chromosome 21 in Down syndrome-derived cells. The goal is to silence the extra copy to limit the gene-dosage imbalance that drives many features of trisomy 21. Researchers at Beth Israel Deaconess Medical Center turned to XIST, the long noncoding RNA responsible for the natural silencing of the X chromosome in females. Using this strategy, they achieved integration efficiencies of 20% to 40% and a partial reduction in the overexpression of chromosome 21 genes.

Trisomy 21, the abnormal third copy of chromosome 21 causing developmental disorders in Down syndrome, has been shown to promote reorganization of the entire neural progenitor cell (NPC) genome, with the resulting gene transcription and cell function disruption being so similar to senescence that anti-senescence drugs could correct them in cell cultures.