Researchers from the South Australian Health and Medical Research Institute (SAHMRI) and the University of Adelaide have uncovered a significant hurdle to realising the potential benefits of gene editing in embryos. North American research published in 2017 seemed to indicate that gene editing in human embryos with so-called molecular scissors, CRISPR-Cas9, was highly effective in repairing defective genes in most embryos. However, the SAHMRI team says their research provides an alternative explanation for the apparent gene corrections, suggesting that the gene editing technology was not fixing small errors, but generating much larger ones. The researchers replicated the North American study in preclinical animal models, as Australia has strict legislation restricting gene editing in human embryos. “We looked beyond the small deletions, exploring larger areas of DNA,” the researchers wrote. “When we searched a wider area, we found that repair of the DNA break generated by ‘molecular scissors’ resulted in deletion of large stretches of DNA.” CRISPR-Cas9 is used by scientists to cut specific regions of a cell’s DNA. Repair of the cut can alter the target DNA sequence, resulting in a specific change or “edit”, so that faulty genes can theoretically be repaired. However, as the SAHMRI researchers have shown, DNA can sometimes be lost during the repair process, resulting in large deletions that would not restore function to the faulty gene. “Understanding the fundamental mechanisms by which these tools work [is an important advancement] for research and for clinical translation to treat a host of genetic diseases.” The SAHMRI research findings were published in Nature.
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