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CRISPR Without Scissors: Modified Gene Editing Tool Can Edit DNA Without Cutting It

The gene editing tool CRISPR-Cas9 helps scientists edit DNA more efficiently and precisely than previously possible. With its ability to cut and paste DNA, the technology offers potentials in one day curing many diseases.

Unfortunately, CRISPR does not always work as scientists expect it to. Sometimes, use of the gene-cutting tool causes off-target effects, which means that for scientists who do gene editing in humans, the mutations produced may unnecessarily cause conditions such as tumors.

Changing Gene's Behavior

Now, researchers have demonstrated a possible workaround. Researchers may not have to edit genes to change the gene's behavior. Researchers from Salk Institute have demonstrated the possibility of changing what genes are expressed sans altering the genome itself.

In experiments involving live mice, researchers successfully used CRISPR to activate beneficial genes in animals that suffer from Type 1 diabetes, acute kidney injury, and muscular dystrophy. Of the animals that had CRISPR intervention, more than 50 percent showed health improvements.

CRISPR System That Lacks Scissors

Instead of using CRISPR/Cas9 to cut apart DNA strands to remove genes or insert new ones, study researcher Hsin-Kai Liao and colleagues used CRISPR as a switch that would simply turn the genes on and off.

The researchers explained that the function that guides the CRISPR system is still there but it essentially lacks the scissors. The new processes used molecular switches to turn specific genes on and off.

Researchers modified the epigenome, chemical compounds that can tell the genome what to do, so it is possible to control the behavior of the genes sans making direct modifications on the DNA. Researchers were able to do this using what's considered a dead form of Cas9. The Cas9 enzyme does the cutting but the dead version does not cut.

Earlier works already showed that CRISPR can alter genes expression in cells but the new study, which was published in the journal Cell, represents the first time that the technique was successfully used in animals. Researchers said that the results of the experiment are significant in that they were able to take a closer step to human therapy.

"We used this technology to treat mouse models of diabetes, muscular dystrophy, and acute kidney disease. Results demonstrate that CRISPR/Cas9-mediated target gene activation can be achieved in vivo, leading to measurable phenotypes and amelioration of disease symptoms," researchers wrote in their study. "This establishes new avenues for developing targeted epigenetic therapies against human diseases."

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