Aug 18, 2019 | Updated: 07:24 AM EDT

Bacteria Provides Breakthroughs in Genome Modification Field

Mar 26, 2015 12:04 PM EDT

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Genetic engineering is not only a hot button issue in the media, but also a crucial tool in biological research. Still one of our primary ways of modeling diseases is by creating mouse models that replicate a human condition. To do that we need genome modification, and a recent rockstar in that area is the CRISPR/Cas system.

It's a mechanism originally found in bacteria, used to defend themselves against viruses. This pair of proteins efficiently and accurately slices DNA at a precise points. In nature it targets viral DNA, but scientists can modify it with relative ease. One component is a strand of RNA that is complementary to the target, all you need to do is modify that RNA and you can cut out virtually any segment of DNA you want.

It's been extremely successful in other bacteria, and even the cell lines of more complex organisms. However, it's still not extremely efficient when attempting to generate transgenic mice, until now. As reported on Physorg, researchers from the Whitehead Institute have found a way to make CRISPR better at modifying zygotes and embryonic stem cells.

When adding or removing a gene using this system, scientists rely on a cell's only DNA repair mechanisms to patch up the cut that CRISPR makes. Two mechanisms are present called non-homologous end joining, and homology-directed repair. The directed repair is more accurate and reliable for engineering, but less commonly used by cells. To shift this natural balance the researchers introduced an anticancer drug during the modification stage. This inhibits the less reliable repair mechanism, increasing the prominence of directed repair and therefore the engineering itself.

Using this mechanism is still in its early stage, and the researchers are hopeful that their techniques will accelerate the development of transgenic mice for modeling disease. But they aren't the only ones making strides, a PLOS ONE paper out of China also made some breakthroughs.

In a highly related piece of work, these researchers were able to modify mice with this system, making extremely large changes. Check the abstract for the full procedure, but the results were the deletion of a gene 65,000 base pairs in length. They were also able to insert a gene 5000 base pairs long. Which is an extremely impressive feat. Both of these breakthroughs will certainly enhance our ability to modify genomes, and hopefully accelerate biomedical research.

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