The CRISPR-Cas9 molecular complex is the tool most widely used by scientists around the world. It cuts double-stranded DNA at the exact point where the genetic material is to be modified. The cut activates two natural repair mechanisms, including homology-directed repair. To induce the cell to use this repair, researchers have recently begun using a molecule called AZD7648, which blocks rapid repair and forces the cell to use homology-directed repair. This approach should accelerate the development of more effective gene therapies. Initial studies on these new approaches have been positive. However, a research group has just discovered that the use of AZD7648 has serious side effects. The modifications would result in the outright deletion of thousands of DNA building blocks, known as bases. Entire chromosome arms were even detached, rendering the genome unstable, with unpredictable consequences for the cells modified by this technique. The study has just been published in the journal Nature Biotechnology.
