Scientists at the Wellcome Sanger Institute have discovered that CRISPR/Cas9 gene editing can cause greater genetic damage in cells than was previously thought. These results create safety implications for gene therapies using CRISPR/Cas9 in the future as the unexpected damage could lead to dangerous changes in some cells.
Reported today (16 July 2018) in the journal Nature Biotechnology, the study also revealed that standard tests for detecting DNA changes miss finding this genetic damage, and that caution and specific testing will be required for any potential gene therapies.
CRISPR/Cas9 is one of the newest genome editing tools. It can alter sections of DNA in cells by cutting at specific points and introducing changes at that location. Already extensively used in scientific research, CRISPR/Cas9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease. Such therapeutics could inactivate a disease-causing gene, or correct a genetic mutation. However, any potential treatments would have to prove that they were safe.
Previous research had not shown many unforeseen mutations from CRISPR/Cas9 in the DNA at the genome editing target site. To investigate this further the researchers carried out a full systematic study in both mouse and human cells and discovered that CRISPR/Cas9 frequently caused extensive mutations, but at a greater distance from the target site.
The researchers found many of the cells had large genetic rearrangements such as DNA deletions and insertions. These could lead to important genes being switched on or off, which could have major implications for CRISPR/Cas9 use in therapies. In addition, some of these changes were too far away from the target site to be seen with standard genotyping methods.
“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.”
Professor Allan Bradley, corresponding author on the study from the Wellcome Sanger Institute
“My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening. Once we realised 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.”
Michael Kosicki, the first author from the Wellcome Sanger Institute
The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers’ interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing.
“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.”
Professor Maria Jasin, an independent researcher from Memorial Slone Kettering Cancer Centre, New York, who was not involved in the study
The Latest on: CRISPR/Cas9
via Google News
The Latest on: CRISPR/Cas9
- The Award of "Scientific Heroines” Honors Dr. Jennifer Doudna on October 4, 2018 at 12:28 pm
The decorated Dr. Doudna, professor in the department of chemistry and chemical engineering and the department of molecular and cell biology at the University of California, Berkeley, is a deserved re... […]
- Domesticating crops usually takes centuries. CRISPR just did it in two years on October 4, 2018 at 11:38 am
CRISPR-Cas9 is useful for all kinds of things, from creating heat-resistant cows to making a potentially limitless supply of transplant organs. Now researchers from Howard Hughes Medical Institute and ... […]
- Better Target Validation for Drug Discovery With CRISPR/Cas9, New Webinar Hosted by Xtalks on October 4, 2018 at 5:32 am
TORONTO, October 4, 2018 (Newswire.com) - Join our keynote speaker, Jon Moore, CSO at Horizon Discovery, for a live session on Tuesday, Oct. 23, 2018. Horizon Discovery has used CRISPR/Cas9 to perform ... […]
- Axcelead Drug Discovery Partners and ERS Genomics Enter into CRISPR/Cas9 License Agreement on October 3, 2018 at 10:00 pm
Axcelead Drug Discovery Partners, Inc.(hereinafter referred to as “Axcelead”) and ERS Genomics Limited (hereinafter referred to as “ERS Genomics”) announced today a non-exclusive license agreement to ... […]
- Yield10 Bioscience Obtains Nonregulated Status for its Novel CRISPR-Cas9 Triple Gene Edited Camelina Plant Lines to Boost Seed Oil Content on October 2, 2018 at 5:00 am
WOBURN, Mass., Oct. 02, 2018 (GLOBE NEWSWIRE) -- Yield10 Bioscience, Inc. (Nasdaq:YTEN), a Company developing new technologies to create step-change improvements in crop yield to enhance global ... […]
- Manifold roles of β-arrestins in GPCR signaling elucidated with siRNA and CRISPR/Cas9 on September 25, 2018 at 11:55 am
1 Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. 2 Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 2942... […]
- Federal Circuit Affirms Board: No Interference-in-Fact for CRISPR-Cas9 Technology on September 21, 2018 at 8:07 am
The Federal Circuit recently weighed in on an interference proceeding between the University of California (“UC”) and the Broad Institute over the use of CRISPR-Cas9 technology. The Court affirmed a P... […]
- University of California Responds to Court of Appeals CRISPR-Cas9 Decision, Vows to Protect Groundbreaking Discovery on September 12, 2018 at 10:09 am
BERKELEY, Calif., Sept. 10, 2018 /PRNewswire/ -- The following statement about today's U.S. Court of Appeals decision on UC's patent interference claim before the Patent Trial and Appeal Board may be ... […]
- CRISPR/Cas9 gene editing scissors are less accurate than we thought, but there are fixes on July 16, 2018 at 1:15 pm
CRISPR gene editing technology is revolutionising medicine and biology. This technique allows scientists to edit DNA with more precision and greater ease than previous gene editing technology. But a n... […]
via Bing News