CRISPR Gene Editing Prompts Chaos In Human DNA

Top Of Formcrispr Gene Editing Prompts Chaos In Dna Of Human Embryosth

Top of Form CRISPR Gene Editing Prompts Chaos in DNA of Human Embryos Three studies identify unintended consequences of gene editing in human embryos, including large deletions and reshuffling of DNA. Amanda Heidt Jun 26, 2020 The ability of CRISPR gene-editing technology to safely modify human embryos has been cast into doubt after several recent papers described massive disruptions to DNA in embryos subjected to editing. Each of the three papers, published this month without peer review on the preprint server bioRxiv , intended to edit only a single gene. But results showed large-scale, unintended DNA deletions and rearrangements in the areas surrounding the targeted sequence. While past research has shown that gene editing can lead to mutations far away from the targeted region, these studies instead draw attention to more localized damage involving larger sequences of DNA that could be overlooked by traditional safety screenings, Nature reports. These studies were intended only for research purposes, meaning the embryos were destroyed after the experiment ended. But in response to their findings, many researchers are voicing their objections to further editing. The field itself is still grappling with the fallout from the birth of twin girls as a result of highly controversial CRISPR experiments carried out by He Jiankui at the Southern University of Science and Technology in China in 2018. “There’s no sugarcoating this,” Fyodor Urnov, a geneticist and CRISPR researcher at the University of California, Berkeley, who was not involved with the research, tells OneZero. “This is a restraining order for all genome editors to stay the living daylights away from embryo editing.” In the first study, published June 5, researchers at the Francis Crick Institute used CRISPR to remove the POU5F1 gene—an important contributor to embryonic development and stem cell pluripotency—in 18 embryos. When they analyzed the effect of the deletion on the genome, they unexpectedly found that eight of these embryos contained additional abnormalities, four of which involved substantial DNA rearrangements and deletions of several thousand base pairs. A second group from Columbia University attempted to modify embryos with a blindness-causing mutation in the EYS gene, the most common gene implicated in the onset of a degenerative eye condition called retinitis pigmentosa. But in addition to the expected changes, they reported on June 18 that almost half of the 23 embryos also lost large chunks of the chromosome on which EYS is located. In the most extreme cases, the chromosome disappeared entirely. Lastly, a study published June 20 by researchers at Oregon Health & Science University similarly focused on correcting a mutation in the MYBPC3 gene that is known to cause a heart condition. While they were successful in repairing the damage in close to half of the 86 embryos—a complement to their pioneering work in 2017 — the authors also reported large disruptions in the chromosome containing the gene. Taken together, these three studies highlight the contrast between off-target effects, which happen when the CRISPR tools edit someplace unintended, and on-target edits, in which the changes are properly localized but have some unintended consequence. In each case, the on-target effects were unexpected. “What that means is that you’re not just changing the gene you want to change, but you’re affecting so much of the DNA around the gene you’re trying to edit that you could be inadvertently affecting other genes and causing problems,” Kiran Musunuru, a cardiologist at the University of Pennsylvania who was not involved in any of the studies, tells OneZero. These problems also show just how little is known about the ways in which the body naturally repairs molecular cuts to the genome made by CRISPR technology, Nature reports. Rather than neatly heal the newly cleaved ends of DNA subjected to editing, the mechanism can sometimes be faulty, leading to degraded or broken DNA. Speaking to Nature, Urnov says these on-target effects warrant the attention of researchers moving forward. “This is something that all of us in the scientific community will, starting immediately, take more seriously than we already have. This is not a one-time fluke.” Downloaded from “The Scientist,” 6/29/2020 Crispr Gene Editing Can Lead to Big Mistakes in Human Embryos Columbia University study of Crispr technology found it made unwanted chromosomal changes in human embryos Scientists still don’t know a lot about the mechanisms of human embryo development. Photo: Kristyna Wentz-Graff/Associated Press By Oct. 29, :00 am ET Scientists using the Crispr gene-editing technology in human embryos to try to repair a gene that causes hereditary blindness found it made unintended and unwanted changes, frequently eliminating an entire chromosome or large sections of it. The study published Thursday in the journal Cell comes as the international scientific community continues to grapple with the potential use of Crispr for editing human embryos that would be intended for creating a pregnancy and birth. In September, an international commission sponsored by the U.S. National Academy of Medicine, U.S. National Academy of Sciences and the U.K.’s Royal Society issued a report stating that the gene-editing technology isn’t ready for such a use because scientists don’t understand how to make precise fixes without also introducing potentially dangerous changes. Dieter Egli, assistant professor of developmental cell biology at Columbia University and the study’s senior author, said, “This study is not going to stop the field. But we have to ask what to do with these powerful tools, and in which context they are safe and efficacious.” Two separate papers published earlier this month indicate that the ethical debate continues over whether and under what circumstances creating genetically modified children could be permissible. One paper, published in the Crispr Journal, solicited views of more than three dozen experts on issues raised in the international commission’s September report on Crispr germ-line editing. The technique—which involves making changes to eggs, sperm and embryos—is controversial because any changes can be passed to future generations. The paper revealed major differences of opinion among leading scholars, including Jennifer Doudna, the University of California, Berkeley, biochemist who with a colleague was awarded the Nobel Prize in chemistry this year for pioneering work on Crispr. In her comments on the report, Dr. Doudna said the commission’s recommendations reflect consensus in the field that the technology shouldn’t be used for embryo editing in the clinic at this time. She added that she was struck by the inclusion of certain diseases that are already being managed, such as cystic fibrosis, with disorders where embryo editing might someday be permissible. The other paper, also published in the Crispr Journal, surveyed policies across 106 countries regarding germ-line gene editing. The researchers found 96 of the countries already had applicable policy documents, such as legislation, regulations or international treaties. Of those 96 countries, 75 bar the use of genetically modified embryos for the purpose of starting a pregnancy—an indication that it might be possible to create an international consensus on the issue. Crispr enables scientists to cut, edit and insert DNA and has been an object of excitement, fascination and controversy since its discovery in 2012. The technology opens up the possibility of treating severe illness for which there are no effective therapies. Trials are under way or expected to start soon in patients with cancer, sickle-cell anemia and other conditions in China, Europe and the U.S. The potential to use Crispr to create genetically modified babies has been an area of major concern, especially after the 2018 announcement of the birth of twin girls from embryos whose DNA had been changed using the Crispr technology. A second woman implanted with a genetically modified embryo is also believed to have given birth. Jennifer Doudna was a co-winner of the Nobel Prize for chemistry this year for pioneering work on Crispr. Photo: uc berkeley handout/handout hand/Shutterstock Very little is known about the health of the babies. He Jiankui, the Chinese researcher who claims to have engineered the birth of the first two genetically tailored humans, said that another woman has been implanted with a genetically modified embryo. The doctor faced criticism from his peers at a gene-editing conference in Hong Kong. Photo: EPA (Originally published Nov. 28, 2018) Write to Amy Dockser Marcus at [email protected] Downloaded from Wall Street Journal online edition, image3.jpeg image1.jpeg image2.jpeg ESSAY 1----- DUE 03/31/23 TOPIC: - Gene Editing: Creating the Designer Human Post are comprised of three elements: 1. Your own original post (OP), responding to the topic as described 1. words 2 pages 2. Your OP should be written in APA format (see the “APA Style Guide” under the “INFORMATION” tab). 3. Sources must be cited. PLAGIARISM WILL NOT BE TOLERATED. 4. Write in a professional way. Do not employ text shorthand, emojis, or the like. FOLLOWING MATERIAL FOR ESSAY 1 READ BOTH FILES: - CRISPR…, Crispr .DOCX Link to readings: Scientists Disagree About the Ethics and Governance of Human Germline Editing - The Hastings Center What are the Ethical Concerns of Genome Editing? MedlinePlus: Genetics Rapidly advancing technologies are creating the potential to alter the human genome by actually changing DNA through techniques known as "gene editing". Just ten years ago, this would have been thought by most to be science fiction. Now it's an emerging science reality. Should we have concerns? It has the promise of providing therapies for debilitating and even fatal illnesses. It also opens the door for creating "designer babies". Want your child to have blue eyes? Want your child to have a superior IQ? Let's explore where all this might lead and discuss the ethical issues that will arise from its use. Carefully review the links in this week's module folder titled "Gene Editing: Creating the Designer Human". You are encouraged to go beyond these links to other resources. In your ESSAY, describe your reactions to what you have learned. Do you think the idea of gene editing is ethical in itself? Do you see it as another medical miracle to be wholeheartedly embraced or should society place limits and controls on its use? If so, what limits would you impose? Be sure to cite your references "in text" and list them at the end of your ESSAY.