The Un-Silencing Of The Genes

Researchers have developed a technique that turns back on silenced, or switched-off, genes without causing unwanted mutations.

AsianScientist (Jul. 15, 2016) – Scientists at Hokkaido University in Japan developed a new technique to unleash silenced genes and change cell fates using the gene-editing technique CRISPR/Cas9.

A revolutionary gene-editing tool, called CRIPSR/Cas9, has made it possible for biological researchers to add, remove or replace specific parts of DNA. Used naturally by bacteria as protection against viruses, CRISPR/Cas9 is the most efficient, inexpensive and easiest gene-editing tool available to date.

In a new study published in the journal Angewandte Chemie International Edition, a research team, led by Professor Toru Kondo at Hokkaido University’s Institute of Genetic Medicine, uses CRISPR/Cas9 to activate genes in the cell.

Genes in cells have their own switches called promoters. A gene is switched off, or silenced, when its promoter is methylated. To turn on a switched-off gene, the team combined a DNA repair mechanism called microhomology-mediated end-joining (MMEJ) with CRISPR/Cas9. They cut out a methylated promoter using CRISPR/Cas9 and then inserted an unmethylated promoter with MMEJ, thus replacing the ‘off switch’ with an ‘on switch.’

To test its effectiveness, the scientists used this tool on cell cultures containing the neural cell gene OLIG2 and the embryonic stem cell gene NANOG. Within five days, they found evidence that the genes were robustly expressed. Furthermore, when they turned on OLIG2 in cultured human stem cells, the cells differentiated to neurons in seven days with high efficiency.

The team also found that their editing tool could be used to activate other silenced promoters. In addition, they found that the system didn’t cause unwanted mutations in other non-targeted genes in the cells.

According to the researchers, potential applications for the tool include manipulating gene expression, creating genetic circuits, or engineering cell fates.


The article can be found at: Katayama et al. (2016) A Powerful CRISPR/Cas9-based Method for Targeted Transcriptional Activation.

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Source: Hokkaido University; Photo: Shutterstock.
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