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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/ is a newly developed tool that allows researchers to easily make changes to an organism's DNA. There is much interest in using this technology in clinical applications, but there have been https://www.physicsforums.com/threads/scientists-identify-major-safety-issue-with-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/.949415/surrounding the safety of the technology, including whether the gene editing approach leads to https://www.physicsforums.com/threads/https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-and-unwanted-dna-alterations.951623/ elsewhere in the genome. Today, two independent teams of researchers developed methods to measure the rate of off target mutations due to CRISPR gene editing and published their results in the journal Science. One team studied the question in mice and another team studied the question in rice, and the two studies came to largely the same conclusions.
The study in mice took embryos that had undergone a single cell division, at which point the embryo consists of only two cells. In once cell, they injected the reagents for CRISPR gene editing along with a marker that would color the cells red, while they left the other cell untreated. After the embryo had developed for a few days, they could then take the embryo, disassociate the cells, sort the red (edited) cells from the uncolored (non-edited) cells, then perform DNA sequencing to detect mutations in each population of cells.
They tested various different CRISPR variants, including thehttps://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/ (which cuts the DNA to introduce errors during repair of the DNA) or 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 directly change DNA base pairs without cutting the DNA). They found that the classic CRISPR method and one type of base editor that can change A-T base pairs to C-G base pairs essentially introduced no detectable off target mutations (the number of new mutations found in the edited cells was indistinguishable from the number of new mutations found in the unedited cells). However, they detected a much higher off target mutation rate for another type of base editor (which changes C-G base pairs to A-T base pairs). The study in rice (which only compared the two types of base editors) found similar results.
The studies indicate that, when correctly deployed, some CRISPR methods can be used for gene editing with minimal risk of off target mutations, and indicated how improvements can be made to some newer base editing technologies (as the C-G base editor was only invented a few years ago, it is likely that improved versions can be developed).
Zuo et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science. Published online 28 Feb 2019. http://science.sciencemag.org/content/early/2019/02/27/science.aav9973
Jin et al. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science. Published online 28 Feb 2019. http://science.sciencemag.org/content/early/2019/02/27/science.aaw7166
Popular press coverage: https://www.wired.com/story/precise-gene-editing-is-trickier-than-expected-but-fixes-are-in-sight/
The study in mice took embryos that had undergone a single cell division, at which point the embryo consists of only two cells. In once cell, they injected the reagents for CRISPR gene editing along with a marker that would color the cells red, while they left the other cell untreated. After the embryo had developed for a few days, they could then take the embryo, disassociate the cells, sort the red (edited) cells from the uncolored (non-edited) cells, then perform DNA sequencing to detect mutations in each population of cells.
They tested various different CRISPR variants, including thehttps://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/ (which cuts the DNA to introduce errors during repair of the DNA) or 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 directly change DNA base pairs without cutting the DNA). They found that the classic CRISPR method and one type of base editor that can change A-T base pairs to C-G base pairs essentially introduced no detectable off target mutations (the number of new mutations found in the edited cells was indistinguishable from the number of new mutations found in the unedited cells). However, they detected a much higher off target mutation rate for another type of base editor (which changes C-G base pairs to A-T base pairs). The study in rice (which only compared the two types of base editors) found similar results.
The studies indicate that, when correctly deployed, some CRISPR methods can be used for gene editing with minimal risk of off target mutations, and indicated how improvements can be made to some newer base editing technologies (as the C-G base editor was only invented a few years ago, it is likely that improved versions can be developed).
Zuo et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science. Published online 28 Feb 2019. http://science.sciencemag.org/content/early/2019/02/27/science.aav9973
Jin et al. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science. Published online 28 Feb 2019. http://science.sciencemag.org/content/early/2019/02/27/science.aaw7166
Popular press coverage: https://www.wired.com/story/precise-gene-editing-is-trickier-than-expected-but-fixes-are-in-sight/
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