Gene editing is a group of technologies/methods used to modify genes in an organism. Gene (or genome) editing can be used to correct, introduce, or delete a section of DNA in an organism’s genome. A commonly used form of gene editing is CRISPR, which stands for clustered regularly interspaced short palindromic repeats; CRISPR-Cas9 is one of the most widely used genome editors, and it is able to defend against harmful viruses by taking small pieces of the virus’s DNA and inserting it into the DNA of the organism. However, it has been reported that CRISPR gene editing may lead to cell toxicity depending on the targeted area.
P-53 is a special protein that can detect mistakes in DNA and prevent those mistakes from harming the cell. The protein can lead cells to stop dividing and trigger programmed cell death, protecting the rest of the body from DNA related issues. Specific spots on targeted genes can lead to an “unwanted p53 effect” which can occur if editing occurs in those areas. The CRISPR gene editing may trigger the p53 when cutting the strands of specific spots on DNA. Edited cells may be marked by the protein as damaged and then destroyed.
The p53 effect resulting from CRISPR gene editing may lead to a bias towards cells with defective p53 proteins. All cells with working p53 would be destroyed as the cut DNA is tagged as damaged. However, cells with dysfunctional p53 would not be destroyed as it isn’t tagged by the p53. As a result, the cell population could favor mutated cells and lead to further mutations. If these specific areas are not avoided, bias towards mutated cells could lead to the development of malignancies and genomic instability.
The most effective way to prevent cell toxicity as a result of gene editing is simply avoiding these “risky spots”. Luckily, investigators have been able to “identify 3,300 places in the human genome where strong toxic effects” may result from CRISPR editing. These regions have been marked with epigenetic markers so that the Cas-9 protein can skip over it and the p53 response can be avoided.
Sources:
Cornall, Jim. “Study Says Gene Editing with CRISPR/Cas9 Can Lead to Cell Toxicity and Genome Instability.” Labiotech.eu, 9 Aug. 2022, https://www.labiotech.eu/trends-news/crispr-gene-editing-toxicity/.
“Gene Editing – Digital Media Kit.” National Institutes of Health, U.S. Department of Health and Human Services, 5 Nov. 2020, https://www.nih.gov/news-events/gene-editing-digital-press-kit.
Leitch, Carmen. “CRISPR/Cas9 Gene Editing Can Be Toxic to Cells & Disrupt Genome Stability: Genetics and Genomics.” Labroots, Labroots, 10 Aug. 2022, https://www.labroots.com/trending/genetics-and-genomics/23360/crispr-cas9-gene-editing-toxic-cells-disrupt-genome-stability.
“What Are Genome Editing and CRISPR-Cas9?: Medlineplus Genetics.” MedlinePlus, U.S. National Library of Medicine, https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/.
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