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Unexpected Outcomes Sound Warning for Embryo Editing

New research led by the South Australian Health and Medical Research Institute and The University of Adelaide has uncovered a significant hurdle for realising the potential benefits of gene editing in embryos.

The team, led by Prof Paul Thomas, investigated North American research published last year that seemed to demonstrate that gene editing in human embryos was highly effective in repairing a defective gene in a majority of the embryos. However, Thomas says their new research, published in Nature (https://goo.gl/tv4HCa), provides an alternative explanation for the apparent gene correction – rather than gene editing technology fixing small errors, much larger errors were being created. “Gene editing technology is still relatively new, and part of this field of research includes understanding the flaws, which will ultimately allow us to develop the safest possible therapies for genetic conditions,” Thomas said.

Australia has strict legislation restricting gene editing in human embryos, so the researchers used preclinical animal models to replicate the North American study. “We looked beyond the small deletions, exploring larger areas of DNA,” said the research paper’s first author, Dr Fatwa Adikusuma. “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.”

The “molecular scissor” technology, CRISPR-Cas9, can cut specific regions of a cell’s DNA, resulting in a specific “edit” that can correct faulty genes. However, Thomas and his colleagues found that DNA can sometimes be lost during the repair process, resulting in large deletions that would not restore function to the faulty gene.

“CRISPR-Cas9 technology is very exciting, with researchers already using it to cure muscular dystrophy in mice, and a number of clinical trials are underway to test gene-editing therapies for several cancers as well as blood diseases,” Thomas said. “Understanding the fundamental mechanisms by which these tools work are important advancements for research and for clinical translation to treat a host of genetic diseases.”