May 29, 2017 CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0) <\/p>\n
As CRISPR-Cas9 starts to move into clinical trials, a new study published in Nature Methods has found that the gene-editing technology can introduce hundreds of unintended mutations into the genome. <\/p>\n
\"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome,\" says co-author Stephen Tsang, MD, PhD, the Laszlo T. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology at Columbia University Medical Center and in Columbia's Institute of Genomic Medicine and the Institute of Human Nutrition. <\/p>\n
CRISPR-Cas9 editing technologyby virtue of its speed and unprecedented precisionhas been a boon for scientists trying to understand the role of genes in disease. The technique has also raised hope for more powerful gene therapies that can delete or repair flawed genes, not just add new genes. <\/p>\n
The first clinical trial to deploy CRISPR is now underway in China, and a U.S. trial is slated to start next year. But even though CRISPR can precisely target specific stretches of DNA, it sometimes hits other parts of the genome. Most studies that search for these off-target mutations use computer algorithms to identify areas most likely to be affected and then examine those areas for deletions and insertions. <\/p>\n
\"These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals,\" says co-author Alexander Bassuk, MD, PhD, professor of pediatrics at the University of Iowa. <\/p>\n
In the new study, the researchers sequenced the entire genome of mice that had undergone CRISPR gene editing in the team's previous study and looked for all mutations, including those that only altered a single nucleotide. <\/p>\n
The researchers determined that CRISPR had successfully corrected a gene that causes blindness, but Kellie Schaefer, a PhD student in the lab of Vinit Mahajan, MD, PhD, associate professor of ophthalmology at Stanford University, and co-author of the study, found that the genomes of two independent gene therapy recipients had sustained more than 1,500 single-nucleotide mutations and more than 100 larger deletions and insertions. None of these DNA mutations were predicted by computer algorithms that are widely used by researchers to look for off-target effects. <\/p>\n
\"Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations,\" Dr. Tsang says. \"Even a single nucleotide change can have a huge impact.\" <\/p>\n
Dr. Bassuk says the researchers didn't notice anything obviously wrong with their animals. \"We're still upbeat about CRISPR,\" says Dr. Mahajan. \"We're physicians, and we know that every new therapy has some potential side effectsbut we need to be aware of what they are.\" <\/p>\n
Researchers are currently working to improve the components of the CRISPR systemits gene-cutting enzyme and the RNA that guides the enzyme to the right geneto increase the efficiency of editing. <\/p>\n
\"We hope our findings will encourage others to use whole-genome sequencing as a method to determine all the off-target effects of their CRISPR techniques and study different versions for the safest, most accurate editing,\" Dr. Tsang says. <\/p>\n
The paper is titled, \"Unexpected mutations after CRISPR-Cas9 editing in vivo.\" Additional authors are Kellie A. Schafer (Stanford University), Wen-Hsuan Wu (Columbia University Medical Center), and Diana G. Colgan (Iowa). <\/p>\n
Explore further: Accurate DNA misspelling correction method <\/p>\n
More information: Unexpected mutations after CRISPR-Cas9 editing in vivo, Nature Methods (2017).<\/p>\n
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If a person has 3 months to live and they use crispr\/cas9 to cure the cancer, and it works, what is the worst than can happen to him? <\/p>\n
I'm not a biologist, so no idea how conceivable or absurd that idea might be. But then there's the whole thing with the Tasmanian devils. Anyway, you asked about worst cases, and that is one possible thing that people who are against this might be thinking. <\/p>\n
Open a door, find 12 new doors. Like the knowledge that carbon nanos caused cancer but the powers-that-be decided we should use it any way because it was so convenient. <\/p>\n
We are so screwed! This is worse than the advent of nuclear weapons. <\/p>\n
this might cause regulated interests to think twice before deploying this for profit. It will not help us at all against weaponized CRISPR, though...<\/p>\n
Crispr is the only way the human race will survive. Without it the machines rule. With crispr the human race increases everyone's IQ 10 fold. The vary smartest of us say \"be very afraid of AI\". Musk likened AI to a devil in a bottle. It's the 2nd level of our most brilliant people that can't see the danger AI poses. Raise everyone's IQ by 10X and we will make much better decisions and solve the current world's problems overnight. <\/p>\n
Meatbrains are passe which is why we are so intent on replacing them. <\/p>\n
Watch Forbidden Planet to see what happens when you mix intelligence with the need to survive to procreate. <\/p>\n
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Excerpt from: May 29, 2017 CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0) As CRISPR-Cas9 starts to move into clinical trials, a new study published in Nature Methods has found that the gene-editing technology can introduce hundreds of unintended mutations into the genome. \"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome,\" says co-author Stephen Tsang, MD, PhD, the Laszlo T Continue reading
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