A new study finds that CRISPR/Cas9 technology leads to unexpected genetic changes

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The widely used gene scissors (CRISPR/Cas) can modify the gene content in cells to study the molecular roles of genes and has gained great clinical importance in gene therapy for the treatment of genetic diseases. A new study, conducted by Claudia Kotter’s research group in the Department of Microbiology, Cells and Tumor Biology at Karolinska Institutet, finds that gene clipping leads to unexpected epigenetic changes.

“We found that CRISPR/Cas9 caused unpredictable targeted genomic effects that affected cancer cell growth. Instead of slowing down, cancer cells grew faster. As CRISPR/Cas genome engineering becomes a popular tool in research and clinical applications, we believe our insights These new findings, together with our innovative and robust approach, will be useful in the evaluation of genetic alterations,” says corresponding author Claudia Kotter, principal investigator in the Department of Microbiology, Cells and Oncology, Karolinska Institutet.

The research team developed a new approach to decode genetic changes with high accuracy and reveal different genetic influences at the target site.

To explain the striking phenotype of the cells, we incorporated the latest technological approaches. First, we specifically enriched our target gene sequence in microdroplets (Xdrop). Second, we read the genetic sequence using nanoscale long read sequencing (ONT-LRS) technology. Finally, we developed a line computationally complex pipelines that decoded minute changes in the genetic sequence,” says first author Keyi Geng, Ph.D. Student in Claudia Kotter’s research group.

The paper was published in Genome research. The research team is now investigating other CRISPR/Cas effects in human cells, with a particular focus on cancer cells that have survived cancer therapies.

“This helps us understand how to repair our genetic material if it is damaged. Although CRISPR/Cas technology is very powerful, we need to find better ways to control CRISPR/Cas activity in human cells. Thus, making CRISPR/Cas technology more Safe to treat patients is a key effort in my group, says Claudia Cotter.

more information:
Keyi Geng et al, Target-enriched nanoscale sequencing and de novo assembly reveal co-replication of complex on-target genome rearrangements induced by CRISPR-Cas9 in human cells, Genome research (2022). DOI: 10.1101/gr.276901.122

Provided by Karolinska Institutet

the quote: New Study Finds CRISPR/Cas9 Leads to Unexpected Genomic Changes (2022, November 14) Retrieved November 15, 2022 from https://phys.org/news/2022-11-crisprcas9-unlimited-genomic.html

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