By Michael Irving
July 04,
2022
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![](https://image.dost-dongnai.gov.vn/english/New%20CRISPR%20tool%20corrects%20mutations%20by%20copying%20genes%20between%20chromosomes.PNG)
A new type
of CRISPR gene-editing tool allows mutations in one chromosome to be corrected
by copying the healthy gene across from the other Photo credit: Depositphotos
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In many
genetic disorders, the defective mutation only occurs on one chromosome, while
the other contains a functional version of that same gene. The new CRISPR tool
corrects the mutation in one chromosome by copying the healthy gene from the
other, a process that the team calls homologous chromosome-templated repair
(HTR).
To
demonstrate the method in action, the team engineered fruit flies with a
visually obvious mutation – pure white eyes, which would form red patches if
the gene editing worked. And sure enough, the red pigment returned in many of
the insects.
The team
found that HTR could be made even more effective if it was paired with
another recent
CRISPR innovation called “nickases.” The usual Cas9 enzyme
cuts both strands of the DNA, which has a lower success rate and can introduce
errors. But nickases just cut one strand of DNA,
allowing the edit to be made more precisely and safely.
A diagram
demonstrating the difference between using CRISPR-Cas9 (left) and CRISPR with
nickases (right) UCSD
In the fruit
fly test, the team showed that CRISPR-Cas9 had a repair success rate of just 20
to 30 percent, often only returning small patches of red to the insects’ eyes
while also introducing frequent off-target mutations. The nickases, on the
other hand, repaired 50 to 70 percent of the targeted genes, restoring eye
color almost back to normal with far fewer unintended mutations.
The team
says that the new technique could eventually be applied to human cells, but
much more work still needs to be done first.
“We don’t
know yet how this process will translate to human cells and if we can apply it
to any gene,” said Annabel Guichard, senior author of the study. “Some
adjustment may be needed to obtain efficient HTR for disease-causing mutations
carried by human chromosomes.”
The research
was published in the journal Science
Advances.
Source: UCSD