The CRISPR-Cas9 gene scissors can precisely alter (human) genes, but can also trigger undesired changes in them. For the first time, researchers at the Ludwig Maximilian University of Munich led by the neurobiologist Professor Dominik Paquet from the Institute of Stroke and Dementia Research were able to easily detect such errors and show, that they occur frequently in stem cells.

CRISPR/Cas9 is widely used in research and is even used for the treatment of patients. Therefore, the technology must be precise and safe. The scientists have now demonstrated that this is not the case.  So-called off-target effects are said to occur in up to 40% of all cells examined.

For their investigations, they have developed a variant of the polymerase chain reaction, called quantitative genotyping PCR (qgPCR), and subjected human induced pluripotent stem cells to closer examination. In addition, they have shown in a cell culture model for Alzheimer's disease that by such unwanted off-target effects no Alzheimer's symptoms appear in vitro at all.

On-target effects may also occur in genetically modified animals because the genetic scissors are used here to "humanize" animals and trigger diseases in them that they normally do not develop. If the desired effects do not occur, they are discarded as useless.

The researchers want to see their technology as a building block for quality control.

Original publication:
Isabel Weisheit, Joseph A. Kroeger, Rainer Malik, Julien Klimmt, Dennis Crusius, Angelika Dannert, Martin Dichgans, Dominik Paquet (2020). Detection of Deleterious On-Target Effects after HDR-Mediated CRISPR Editing. Cell Reports. https://www.sciencedirect.com/science/article/pii/S2211124720306422

Source:
https://www.bionity.com/de/news/1166489/genschere-crispr-cas9-schnitt-mit-nebenwirkung.html?pk_campaign=ca0264&WT.mc_id=ca0264