Getting real: CRISPR-Cas9 gene editing causes lots of mutations | Science| In-depth reporting on science and technology | DW | 19.07.2018
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Getting real: CRISPR-Cas9 gene editing causes lots of mutations

A British study shows that gene editing does not work as well as previously assumed. Experiments using the cells of mice and humans resulted in numerous unwanted mutations.

The molecular biological gene editing CRISPR/Cas9 method regularly causes unwanted mutations. This also happens in areas of the genome far from the target areas that medical researchers and molecular biologists may seek to change using this promising innovative tool.

That is the sobering result of a study by molecular biologists Michael Kosicki, Kärt Tomberg and Allan Bradley of the Wellcome Sanger Institute in Hinxton, UK.The study was published in the journal"Nature Biotechnology" on July 16.

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The discoverer of "enzyme scissors"

Great expectations in medicine and biology

Since the discovery of CRISPR-Cas9 by Emmanuelle Charpentier and Jennifer Doudna in 2011, gene editing has been considered a decisive scientific breakthrough by medical doctors and molecular biologists.

The doctors hope that cutting out individual genes with high-precision will help correct genetic diseases such as sickle cell anaemia.

Gene editing can theoretically also be used in plant breeding and numerous other areas of molecular biological research. But it is probably not that simple in practice.

Not the entire genome in view

The authors note that so far "exploration of Cas9-induced genetic alterations has been limited to the immediate vicinity of the target site and distal off-target sequences, leading to the conclusion that CRISPR–Cas9 was reasonably specific."

Mikroinjektion (picture-alliance/dpa/Max-Delbrück-Centrum für Molekulare Medizin)

Gene editing with Zebrafish emryos: Similar tests with mice cells resulted in unwanted mutations

But now the researchers have carried out what is known as "long-read sequencing and long-range PCR genotyping." This means they use the polymerase chain reaction (PCR) technique, which is usually used to multiply gene segments, and then analyze individual genes to examine larger areas of the genome after the use of gene scissors.

And they found that the use of CRISPR/Cas9 also leads to extinction and damage very far from the desired target region.

New diseases as a result?

According to the researchers, this damage could have "pathogenetic consequences," which can in turn cause new hereditary diseases.

The researchers used mouse embryonic stem cells, mouse hematopoietic progenitors and a human differentiated cell line for their experiments.

The authors of the study warn that physicians who want to use CRISPR/Cas9 should be particularly careful. Further research is necessary and the possible side-effects should not be underestimated.

 

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