Genome-editing tool could increase cancer risk

June 11, 2018, Karolinska Institutet
Bernhard Schmierer, research team leader at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. Credit: Ulf Sirborn

Therapeutic use of gene editing with the CRISPR-Cas9 technique may inadvertently increase the risk of cancer, according to a new study from Karolinska Institutet, Sweden, and the University of Helsinki, Finland, published in Nature Medicine. Researchers say that more studies are required in order to guarantee the safety of these 'molecular scissors' for gene-editing therapies.

CRISPR-Cas9 is a molecular machine first discovered in bacteria that can be programmed to go to an exact place in the genome, where it cuts the DNA. These precise 'molecular scissors' can be used to correct faulty pieces of DNA and are currently being used in clinical trials for cancer immunotherapy in the U.S. and China. New trials are expected to be launched soon to treat inherited blood disorders such as sickle cell anaemia.

Two independent articles published in the journal Nature Medicine now report that therapeutic application of the genome-editing tool may, in fact, increase the risk of cancer. In one of the studies, scientists from Karolinska Institutet and the University of Helsinki report that use of CRISPR-Cas9 in human cells in a laboratory setting can activate a protein known as p53, which acts as a cell's 'first aid kit' for DNA breaks. Once active, p53 reduces the efficiency of CRISPR-Cas9 gene editing. Thus, cells that do not have p53 or are unable to activate it show better gene editing. Unfortunately, however, lack of p53 is also known to contribute to making cells grow uncontrollably and become cancerous.

"By picking cells that have successfully repaired the damaged gene we intended to fix, we might inadvertently also pick cells without functional p53," says Dr. Emma Haapaniemi, researcher at the Department of Medicine at Karolinska Institutet in Huddinge and co-first author of the study. "If transplanted into a patient, as in gene therapy for inherited diseases, such cells could give rise to cancer, raising concerns for the safety of CRISPR-based gene therapies."

"CRISPR-Cas9 is a powerful tool with staggering therapeutic potential," adds Dr. Bernhard Schmierer, researcher at the Department of Medical Biochemistry and Biophysics at Karolinska Institute, who co-supervised the study. "Like all medical treatments however, CRISPR-Cas9-based therapies might have side effects, which the patients and caregivers should be aware of. Our study suggests that future work on the mechanisms that trigger p53 in response to CRISPR-Cas9 will be critical in improving the safety of CRISPR-Cas9-based therapies."

Explore further: Genome editing method targets AIDS virus

More information: Emma Haapaniemi et al, CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response, Nature Medicine (2018). DOI: 10.1038/s41591-018-0049-z

Related Stories

Genome editing method targets AIDS virus

May 18, 2018
By destroying the regulatory genes of the AIDS virus HIV-1 using the genome editing system CRISPR/Cas9, a Japanese research group has succeeded in blocking the production of HIV-1 by infected cells.

CAR T cells more powerful when built with CRISPR, researchers find

February 22, 2017
Researchers from Memorial Sloan Kettering Cancer Center (MSK) have harnessed the power of CRISPR/Cas9 to create more-potent chimeric antigen receptor (CAR) T cells that enhance tumor rejection in mice. The unexpected findings, ...

Recommended for you

Shared genetics may shape treatment options for certain brain disorders

June 20, 2018
Symptoms of schizophrenia and bipolar disorder, including psychosis, depression and manic behavior, have both shared and distinguishing genetic factors, an international consortium led by researchers from Vanderbilt University ...

Simple sugar delays neurodegeneration caused by enzyme deficiency

June 20, 2018
A new therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB). Neurodegeneration in this condition results from the abnormal accumulation of essential cellular ...

Scientists unravel DNA code behind rare neurologic disease

June 20, 2018
Scientists conducting one of the largest full DNA analyses of a rare disease have identified a gene mutation associated with a perplexing brain condition that blinds and paralyzes patients.

Targeting the engine room of the cancer cell

June 18, 2018
Researchers at Columbia University Irving Medical Center (CUIMC) have developed a highly innovative computational framework that can support personalized cancer treatment by matching individual tumors with the drugs or drug ...

Scientists learn more about how gene linked to autism affects brain

June 18, 2018
New preclinical research shows a gene already linked to a subset of people with autism spectrum disorder is critical to healthy neuronal connections in the developing brain, and its loss can harm those connections to help ...

161 genetic factors for myopia identified

June 15, 2018
The international Consortium for Refractive Error and Myopia (CREAM) recently published the largest-ever genetic study of myopia in Nature Genetics. Researchers from the Gutenberg Health Study at the Medical Center of Johannes ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.