JUL 17, 2018 10:42 AM PDT

CRISPR can Seriously Damage the Genome

WRITTEN BY: Carmen Leitch

The CRISPR/Cas9 gene-editing system took the research world by storm when it was first introduced. With just a few simple reagents inspired by an immune defense system in bacteria, researchers learned how to make edits to the genome, in a method that seemed straight-forward and ripe with possibilities. While some of them are being realized, new research is tempering our expectations. Some work has shown that the CRISPR editor might increase the risk of cancer. Another new study has found that the process makes more extensive changes than we knew, causing serious damage to the genome of cells growing in culture.

Scientists at the Wellcome Sanger Institute have found that the typical techniques that check for genomic damage can miss what they are seeing - big deletions and insertions after CRISPR is used. Reporting in Nature Biotechnology, they urge caution especially when using CRISPR for human gene therapies.

 "This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now. It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects,” said the corresponding study author, Professor Allan Bradley of the Wellcome Sanger Institute.

In this work, the researchers looked for unintended mutations, also called off-target effects, of the CRISPR/Cas9 tool. Not many have been observed near the region targeted for changes, so the investigators looked further afield. In both human and mouse cells, they found frequent and extensive mutations far from the intended edit site.

Many of those mutations were found to be big rearrangements, in which large chunks of DNA are inserted or removed from the genome. That could have many potential negative effects on gene expression. 

Related: Concerns About the CRISPR/Cas9 Gene Editor

"My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however, it became clear that something unexpected was happening,” explained first author Michael Kosicki of the Wellcome Sanger Institute. “Once we realized the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines, and showed that the CRISPR/Cas9 effects held true."

Certainly, this and other related findings will force a reassessment of the CRISPR technology and will probably lead scientists to continue to look for reliable ways to manipulate the genome.

"This study is the first to assess the repertoire of genomic damage arising at a CRISPR/Cas9 cleavage site. While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically,” concluded Professor Maria Jasin of Memorial Slone Kettering Cancer Centre, New York, who was not a part of this work. 

Sources: AAAS/Eurekalert! Via Wellcome Trust Sanger Institute, Nature Biotechnology

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
SEP 28, 2020
Genetics & Genomics
Why Some Young, Healthy People Get Severe COVID-19
SEP 28, 2020
Why Some Young, Healthy People Get Severe COVID-19
Since the start of the pandemic, scientists have been trying to find out why some people get such severe illness from SA ...
OCT 04, 2020
Genetics & Genomics
The Intriguing Genome of Mitochondria
OCT 04, 2020
The Intriguing Genome of Mitochondria
Our cells carry special structures called organelles, with each different organelle performing various specialized, crit ...
OCT 19, 2020
Cancer
Using qPCR to Diagnose Common Cancer Mutations in Lung Cancer
OCT 19, 2020
Using qPCR to Diagnose Common Cancer Mutations in Lung Cancer
Cancer is a disease characterized by DNA mutations. These mutations, while sometimes small, can cause havoc in a cell&rs ...
OCT 19, 2020
Genetics & Genomics
Early Childhood Trauma Affects Metabolism in the Next Generation
OCT 19, 2020
Early Childhood Trauma Affects Metabolism in the Next Generation
Traumatic experiences can have a lasting impact, and kids that suffer through them can feel the effects for a lifetime. ...
NOV 03, 2020
Genetics & Genomics
One Eight Cancer Patients Also Carry Inherited Genetic Mutations
NOV 03, 2020
One Eight Cancer Patients Also Carry Inherited Genetic Mutations
Genetic sequencing technologies have rapidly advanced, reducing the time required to sequence the entire human genome fr ...
NOV 14, 2020
Cannabis Sciences
New Genetic Test Identifies Cannabis THC Levels from Seeds
NOV 14, 2020
New Genetic Test Identifies Cannabis THC Levels from Seeds
Researchers from the University of Minnesota have developed a genetic test that can predict how much cannabidiol (CBD) o ...
Loading Comments...