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https://www.physicsforums.com/insights/dont-fear-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-new-gene-editing-technologies-wont-lead-designer-babies/provides scientists with an easy way to introduce targeted genetic changes to DNA and a number of different companies are looking at ways to use CRISPR to fix genetic diseases in humans. Two groups of researchers, however, have identified a major issue with CRISPR gene editing that has important implications for the safety of the technique.
CRISPR-Cas9 is an enzyme that cuts the DNA inside of the cell at a specific location. After the DNA is cut, scientists can then manipulate the cellular DNA repair systems to introduce mutations at the site of the cut to inactivate a specific gene or introduce foreign DNA sequences at the site of the cut to, for example, fix a disease causing mutation. Normal cells, however, have defenses against DNA damage, including the tumor suppressor protein p53. The researchers found that active p53 proteins inside of the cell greatly reduce the efficiency of gene edits by CRISPR. What this means, however, is that the cells that are successfully edited often have problems with their p53.
Why is this important? p53 helps protect cells against cancer:
If selecting for edited cells selects for cells with defective p53, those cells will likely have an increased propensity to become cancerous in the future.
Small scale studies of CRISPR have not been able to detect increases in cancer, so it is possible that these studies do not tell the whole story. Furthermore, these problems may not occur in some applications of CRISPR (disrupting genes) and may mainly affect cases where scientists are using CRISPR to repair genes. There are also newer technologies that can https://www.physicsforums.com/threads/https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-based-base-changes.930803/, which would not be subject to these concerns. Still, these papers point out important limitations in CRISPR technology that need to be considered as CRISPR moves towards clinical applications.
Primary scientific literature:
Haapaniemi et al. 2018 CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response. Nature Medicine. Published online 11 June 2018. https://www.nature.com/articles/s41591-018-0049-z
https://www.biorxiv.org/content/early/2017/08/25/180943
Ihry et al. 2018. p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells. Nature Medicine. Published online 11 June 2018. https://www.nature.com/articles/s41591-018-0050-6
https://www.biorxiv.org/content/early/2017/07/26/168443
Popular press:
STAT news: https://www.statnews.com/2018/06/11...chnologies-wont-lead-designer-babies/']crispr-hurdle-edited-cells-might-cause-cancer/[/URL]
CRISPR-Cas9 is an enzyme that cuts the DNA inside of the cell at a specific location. After the DNA is cut, scientists can then manipulate the cellular DNA repair systems to introduce mutations at the site of the cut to inactivate a specific gene or introduce foreign DNA sequences at the site of the cut to, for example, fix a disease causing mutation. Normal cells, however, have defenses against DNA damage, including the tumor suppressor protein p53. The researchers found that active p53 proteins inside of the cell greatly reduce the efficiency of gene edits by CRISPR. What this means, however, is that the cells that are successfully edited often have problems with their p53.
Why is this important? p53 helps protect cells against cancer:
https://www.statnews.com/2018/06/11...chnologies-wont-lead-designer-babies/']crispr-hurdle-edited-cells-might-cause-cancer/[/URL]The reason why that could be a problem is that p53 dysfunction can cause cancer. And not just occasionally. P53 mutations are responsible for nearly half of ovarian cancers; 43 percent of colorectal cancers; 38 percent of lung cancers; nearly one-third of pancreatic, stomach, and liver cancers; and one-quarter of breast cancers, among others.
If selecting for edited cells selects for cells with defective p53, those cells will likely have an increased propensity to become cancerous in the future.
Small scale studies of CRISPR have not been able to detect increases in cancer, so it is possible that these studies do not tell the whole story. Furthermore, these problems may not occur in some applications of CRISPR (disrupting genes) and may mainly affect cases where scientists are using CRISPR to repair genes. There are also newer technologies that can https://www.physicsforums.com/threads/https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-based-base-changes.930803/, which would not be subject to these concerns. Still, these papers point out important limitations in CRISPR technology that need to be considered as CRISPR moves towards clinical applications.
Primary scientific literature:
Haapaniemi et al. 2018 CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response. Nature Medicine. Published online 11 June 2018. https://www.nature.com/articles/s41591-018-0049-z
https://www.biorxiv.org/content/early/2017/08/25/180943
Ihry et al. 2018. p53 inhibits CRISPR–Cas9 engineering in human pluripotent stem cells. Nature Medicine. Published online 11 June 2018. https://www.nature.com/articles/s41591-018-0050-6
https://www.biorxiv.org/content/early/2017/07/26/168443
Popular press:
STAT news: https://www.statnews.com/2018/06/11...chnologies-wont-lead-designer-babies/']crispr-hurdle-edited-cells-might-cause-cancer/[/URL]
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