Over the past decade, the CRISPR-Cas9 gene editing system has revolutionized genetic engineering, allowing scientists to make targeted changes to organisms’ DNA. While the system could potentially be useful in treating a variety of diseases, CRISPR-Cas9 editing involves cutting DNA strands, leading to permanent changes to the cell’s genetic material. Although scientists have successfully used CRISPR-Cas9 to make genetic changes in practice, most has involved a fixed and limited set of genetic sequences. This limited set has led to a DNA-structure limitation hard to achieve with larger DNA edits.

A new study, published online August 17 in the journal Nature, aims to develop a system that can accommodate an unlimited amount of information about the genome. The new genome editing system has the potential to overcome some of the limitations of CRISPR-Cas9, making it possible to easily edit genomes of undesired effect and to create examples that can be readily reproducible.

In this latest study in Nature, Changzhen University, China's leading research institution, researchers originated a new primary structure, designated in the paper as m2x2, but formally called an edge chain, which they think gives the structure enough flexibility to support gene editing.

"Previous work has suggested that an m2x2 edge concept may be where it's at with this gene editing concept," says Sumever Khot, past president of the Center for Computational Molecular Biology at the University of Washington and coauthor of the paper. "Because it works for any fixed length of DNA, we believe its primary function will be to serve as a bridge between a second structure potentially corresponding to a larger gene edit and the speed of gene editing."

Using the new edge locus to link two two-dimensional basic building blocks, scientists can reshape a DNA molecule. Khot and fellow researchers Kisho Takahashi and Nikolay Vinessavskii, who cofounded the team, believe the main idea behind the system, however, is simple. They do not believe gene editing should involve large changes to the cell´s basic physiology. That was the thinking behind attempting to design a system that was more flexible and less risky.

"In the past, gene editing was done in one of two ways," says Igor Rubinstein, a senior research scientist in Khot's lab and lead author of the paper. "One way was a cut and paste approach that can't be closed and burned in, like capturing UV light and editing DNA directly with a UV light source. The other was applying a nuclear transfer approach where the cell divides and inserts or destroys the edited DNA."

Both of those solutions proved to be the limit for CRISPR-Cas9. The authors say that adding a third genetic structure, edites by adding or removing nucleotides, might allow gene editing
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