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New Gene-Editing Technique Can Alter Genome Without Cutting DNA

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A team of researchers from MIT and Harvard found a way to make the CRISPR gene-editing system safer and more accurate.

In a study, they proposed a system that can insert new DNA sequences without making any cuts and therefore prevent any unwanted side effects from manifesting. The system has potential to enable a more efficient gene insertion than current technologies, which have many limitations and are prone to errors.

A New Way To Wield The CRISPR Tool

Instead of relying on a defensive enzyme like Cas9, the researchers turned to transposons, also known as "jumping genes." Transposons are DNA sequences known for their tendency to jump around in the genome. They are guided by proteins called transposases that insert the DNA into a target site without cutting and pasting.

For the study, the researchers isolated the enzyme Cas12k from two species of cyanobacteria and manipulated them to jump into genome to set targets. Then they insert new DNA sequences without having to remove sections.

They called the new system CRISPR-associated transposase or CAST.

"We dove deeply into this system in cyanobacteria, began taking CAST apart to understand all of its components, and discovered this novel biological function," said Jonathan Strecker, a postdoctoral fellow at the Broad Institute of MIT and the first author of the study. "CRISPR-based tools are often DNA-cutting tools, and they're very efficient at disrupting genes. In contrast, CAST is naturally set up to integrate genes."

The team tested CAST on E. coli. They programed the new system to introduce new DNA sequence (up to 10 base pairs long) into specific targets on the genome.

They reported an 80 percent success rate, which they said could still be improved after further research.

Real-Life Application

The researchers envisions the new technique being used in a myriad of ways, particularly to treat genetic diseases. They mentioned sickle cell disease, an inherited disease that result to abnormality in the hemoglobin, which delivers oxygen throughout the body. Sickle cell disease causes sickle or crescent-shaped red blood cells

CAST could be used to integrate a healthy version of a gene into the genome and override the one that is causing the problem.

They described the new system in the journal Science.

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