Alarming findings in cancer gene therapy

Scientists have discovered that CRISPR-Cas9 gene editing can cause leukemia-derived cancer cells to remove important genes under stress. This neglected phenomenon affects gene regulation and has major implications for cancer treatment and research, highlighting the need for precise use of gene editing techniques.

New research reveals that CRISPR-Cas9 gene editing can inadvertently cause cancer cells to remove important genes, impacting cancer research and treatment strategies.

A new study by Claudia Kotter's research group in the Department of Microbiology, Oncology and Cell Biology (MTC) has identified potential risks in using CRISPR-Cas9 gene editing technology, the gene scissors used to treat cancer.

The study determined that the cancer cell line, derived from leukemia, removes the region that encodes a tumor suppressor gene and genes that control cell growth.

“We have found that this elimination often occurs when cancer cells are exposed to stress, such as when using CRISPR, gene scissors, or other treatments such as antibiotics. Elimination changes gene regulation in a unique way, which in turn affects basic biological processes such as DNA Replication, cell cycle regulation, and DNA repair,” says Claudia Kotter, research group leader at MTC, Karolinska Institutet.

Implications for cancer research and treatment

This knowledge is important for researchers, clinicians, and biotechnologists to correctly interpret and apply gene editing results. The study also has clinical significance, as the observed deletions are found in genes associated with cancer, which has implications for cancer research and treatment.

“Shockingly, this removal was inadvertently overlooked by many researchers who edited genes in cancer cells through CRISPR assays. The removal also occurred more frequently in patients undergoing cancer treatment. The cancer cells had “The treatment, because of the removal, has a selective advantage, which is bad for the patient's long-term survival as these cells remain after treatment.”

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A call for cautious progress

“The study is primarily a warning signal, but it also opens the doors to further research aimed at harnessing the potential of gene editing while minimizing unintended consequences,” Claudia concluded.

Reference: “Intrinsic deletion at 10q23.31, incl Button Gene locus, exacerbated by CRISPR-Cas9-mediated genome engineering in HAP1 cells mimicking cancer profiles” by Qi Jing, Lara J. Merino, Raul J. Vega, Christian Sommerauer, Janine Eberlein, Eva K. Brinkmann, and Claudia Kotter, November 20, 2023, Life Sciences Alliance.
doi: 10.26508/lsa.202302128

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