CRISPR/Cas9 Awakens Silenced Genes

A method combining microhomology-mediated end-joining (MMEJ) with the gene-editing technology CRISPR/Cas9 demonstrated the ability to activate switched-off or silenced genes in a study conducted by Hokkaido University.

Genes become silenced when their promoters are methylated. In order to switch the genes back on, researchers cut out a methylated promoter using CRISPR/Cas9, and then inserted an unmethylated promoter with MMEJ, replacing the off-switch with an on switch.

To test the tool’s efficiency in cultured cells, researchers tested it on the embryonic stem cell gene NANOG and the neural cell gene OLIG2.

The results of the study showed that within 5 days, there was evidence of genes being robustly expressed. Once the OLIG2 was turned on in cultured human stem cells, the cells differentiated to neurons with high efficiency in 7 days.

The results indicate the editing tool could be used to activate other silenced promoters. The study further revealed the system did not cause any unwanted mutations in other non-targeted genes.

The study concluded the editing tool has the ability to engineer cell fates, create genetic circuits, and manipulate gene expression.