{"id":4845,"date":"2019-11-15T15:01:20","date_gmt":"2019-11-15T06:01:20","guid":{"rendered":"http:\/\/163.180.4.222\/lab\/?p=4845"},"modified":"2019-11-15T15:04:09","modified_gmt":"2019-11-15T06:04:09","slug":"crispr-tool-modifies-genes-precisely-by-copying-rna-into-the-genome","status":"publish","type":"post","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4845","title":{"rendered":"CRISPR tool modifies genes precisely by copying RNA into the genome &#038; CRISPR: the movie"},"content":{"rendered":"<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h5>The ultimate goal of genome editing is to be able to make any specific change to the blueprint of life. A \u2018search-and-replace\u2019 method for genome editing takes us a giant leap closer to this ambitious goal.<\/h5>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<div class=\"article__body serif cleared\">\n<p>Variation in the DNA sequences that constitute the blueprint of life is essential to the fitness of any species, yet thousands of DNA alterations are thought to cause disease. After decades of research in genetics and molecular biology, tremendous progress has been made in developing genome-editing tools for correcting such alterations. But a seemingly fundamental limit to the efficiency and precision of gene editing was reached, owing to the tools\u2019 reliance on complex and competing cellular processes.\u00a0<a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1711-4\" data-track=\"click\" data-label=\"https:\/\/www.nature.com\/articles\/s41586-019-1711-4\" data-track-category=\"body text link\">Writing in\u00a0<i>Nature<\/i><\/a>, Anzalone\u00a0<i>et al.<\/i><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR1\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">1<\/a><\/sup>\u00a0describe \u2018search-and-replace\u2019 genome editing, in which the marriage of two molecular machines enables the genome to be altered precisely. The technique has immediate and profound implications for the biomedical sciences.<\/p>\n<p>&nbsp;<\/p>\n<aside class=\"recommended pull pull--left sans-serif\" data-label=\"Related\"><a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1711-4\" data-track=\"click\" data-track-label=\"recommended article\"><img decoding=\"async\" class=\"recommended__image\" src=\"https:\/\/media.nature.com\/w400\/magazine-assets\/d41586-019-03392-9\/d41586-019-03392-9_17365626.jpg\" \/><\/a><\/p>\n<p class=\"recommended__title serif\">Read the paper: Search-and-replace genome editing without double-strand breaks or donor DNA<\/p>\n<\/aside>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>Human efforts to engineer genomes pre-date knowledge of genes or even of the source of heredity. The first genome engineering relied on natural variation and artificial selection through selective breeding. Modern maize (corn), for example, was \u2018engineered\u2019 from its wild ancestor, teosinte, through artificial selection more than 9,000 years ago<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR2\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">2<\/a><\/sup>. Later progress was fuelled by the realization that DNA sequences shape life, and that evolution can be augmented and artificially accelerated through the use of mutagenic agents, such as radiation or chemicals.<\/p>\n<p>Next came the discovery that cellular processes for repairing mistakes in DNA sequences could be hijacked, allowing sequences from a foreign \u2018template\u2019 DNA to be inserted into the genome at DNA breaks<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR3\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">3<\/a><\/sup>. This process is greatly enhanced if the DNA is intentionally damaged<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR4\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">4<\/a><\/sup><sup>,<\/sup><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR5\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">5<\/a><\/sup>\u00a0\u2014 a finding that sparked a search of more than 20 years for an enzyme that could specifically cut DNA at locations of interest. The search culminated in the adoption of the bacterial CRISPR\u2013Cas9 system, in which the enzyme Cas9 uses a customizable RNA guide to search for DNA sequences to cut in human cells<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR6\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">6<\/a><\/sup><sup>\u2013<\/sup><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR8\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">8<\/a><\/sup>\u00a0(Fig. 1a).<\/p>\n<p>&nbsp;<\/p>\n<figure class=\"figure\">\n<div class=\"embed intensity--high\">\n<div class=\"embed intensity--high\"><img decoding=\"async\" class=\"figure__image\" src=\"https:\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-03392-9\/d41586-019-03392-9_17372794.png\" alt=\"\" data-src=\"\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-03392-9\/d41586-019-03392-9_17372794.png\" \/><\/div>\n<\/div><figcaption>\n<p class=\"figure__caption sans-serif\"><span class=\"mr10\"><b>Figure 1 | Evolution of genome editing.<\/b>\u00a0<b>a<\/b>, In conventional genome editing, a Cas9 enzyme is directed to a position in the genome by a guide RNA, and produces a double-strand break. The host cell\u2019s DNA-repair machinery fixes the break, guided by a template DNA, incorporating template sequences into the duplex.\u00a0<b>b<\/b>, In an approach called base editing, a Cas9 that produces only single-strand breaks (nicks) works with a deaminase enzyme. The deaminase chemically modifies a specific DNA base \u2014 here, a cytidine base (C) is converted to uracil (U). DNA repair then fixes the nick and converts a guanine\u2013uracil (G\u2013U) intermediate to an adenine\u2013thymine (A\u2013T) base pair. This method is more precise than\u00a0<b>a<\/b>, but makes only single-nucleotide edits.\u00a0<b>c<\/b>, Anzalone\u00a0<i>et al<\/i>.<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR1\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">1<\/a><\/sup>\u00a0report prime editing, which can precisely edit DNA sequences. A nick-producing Cas9 and a reverse transcriptase enzyme produce nicked DNA into which sequences corresponding to the guide RNA have been incorporated. The original DNA sequence is cut off, and DNA repair then fixes the nicked strand to produce a fully edited duplex. In some cases, another nick is made in the unedited strand of the duplex before the DNA-repair step (not shown).<\/span><\/p>\n<\/figcaption><\/figure>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>CRISPR\u2013Cas9 sparked a revolution in the biomedical sciences by making genome editing accessible to all researchers, but, ultimately, it is just a fancy pair of molecular scissors that cuts DNA. Because cuts in DNA are deadly to cells, they are urgently repaired by one of many independent pathways. In the context of genome editing, the desired outcome is for repair to be directed by a template DNA, resulting in precise edits. But most cells prefer to use an alternative mechanism, in which the DNA template is ignored and the two broken ends of DNA are imperfectly stitched back together \u2014 a major limitation for genome editing.<\/p>\n<p>Much effort over the past few years has focused on shifting the balance from imperfect to precise editing. One effective strategy is to edit DNA without cutting both DNA strands in the helix \u2014 double-strand breaks are the main insult that leads to imperfect edits. A milestone in this regard was the development of base editing<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR9\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">9<\/a><\/sup>, a process in which a version of the Cas9 enzyme that cuts only one DNA strand is combined with an enzyme that can switch one specific DNA base for another, near the nick site (Fig. 1b). However, the technical constraints of base editing, and the need to modify more than just single DNA bases, meant that new genome-editing approaches were still desperately needed.<\/p>\n<p>Anzalone and co-workers now largely fill this need with a technique called prime editing. Their approach relies on a hybrid molecular machine consisting of a modified version of Cas9, which cuts only one of the two DNA strands, and a reverse transcriptase enzyme, which installs new and customizable DNA at the cut site (Fig. 1c). This marriage parallels a naturally occurring process in yeast, in which DNA that corresponds to an RNA sequence is incorporated into the genome by a reverse transcriptase<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR10\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">10<\/a><\/sup>.<\/p>\n<p>The prime-editing process is orchestrated by an engineered, two-part RNA guide. The \u2018search\u2019 part of the guide directs Cas9 to a specific sequence in the DNA target, where it cuts one of the two DNA strands. The reverse transcriptase then produces DNA complementary to the sequence in the \u2018replace\u2019 part of the RNA guide, and installs it at one of the cut DNA ends, where it takes the place of the original DNA sequence.<\/p>\n<aside class=\"recommended pull pull--left sans-serif\" data-label=\"Related\"><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01824-0\" data-track=\"click\" data-track-label=\"recommended article\"><img decoding=\"async\" class=\"recommended__image\" src=\"https:\/\/media.nature.com\/w400\/magazine-assets\/d41586-019-03392-9\/d41586-019-03392-9_17365620.jpg\" \/><\/a><\/p>\n<p class=\"recommended__title serif\">Hijack of CRISPR defences by selfish genes holds clinical promise<\/p>\n<\/aside>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>At this point, the duplex DNA being modified consists of two non-complementary strands: the edited strand, and the intact strand that wasn\u2019t cut by Cas9. Non-complementary sequences are not tolerated in cells, so one of the strands must be fixed by DNA-repair processes to match the other, with the intact strand typically being preferentially retained. The authors therefore usually had to use a second RNA guide to direct a cut to the intact strand, to increase the chances that that strand would be repaired to match the edited sequence. The cut must be made strategically to avoid breaking both strands at the same time or place.<\/p>\n<p>Anzalone\u00a0<i>et al<\/i>. demonstrate the versatility of prime editing by using it to efficiently and precisely install a wide range of sequences into DNA. For example, they used it\u00a0<i>in vitro<\/i>\u00a0in human embryonic kidney cells to correct the mutations that give rise to the blood disorder sickle-cell disease, and to edit the mutations that cause the neurological condition Tay\u2013Sachs disease. Imperfect edits were almost entirely avoided. The authors also carried out edits in human cancer cells and in mouse neurons<i>\u00a0in vitro<\/i>.<\/p>\n<p>For decades, the potential of genome editing has been constrained by the difficulty of making precise modifications, and so applications have focused heavily on situations in which imperfect DNA edits are useful. For example, such edits can be used to impair the function of a gene, providing an avenue for understanding its function<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR11\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">11<\/a><\/sup>. Prime editing now makes it faster and easier than before to install or correct one or many specific mutations (such as those found in human patients, or synthetic sequences that are useful for research purposes). And it makes more cell types available for manipulation than was previously possible. The chains that have shackled gene editing have thus come off \u2014 no doubt quickening the pace of research and enabling a list of new applications.<\/p>\n<p>Nevertheless, prime editing has limitations. First, the sophisticated, multi-step molecular dance that occurs between the prime-editing components is not yet predictable and doesn\u2019t always turn out as intended. Imperfect random edits can therefore still arise, which means that several combinations of components might need to be tested, to work out the choreographies required for each edit of interest. Second, delivering the large prime-editing system into some cell types could be challenging, given that many previous attempts have faltered with the conventional Cas9 system<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR12\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">12<\/a><\/sup>, which is roughly half the size.<\/p>\n<p>For research purposes, these limitations are mostly just inconvenient, and will probably be overcome through follow-up work directed at better understanding and fine-tuning the method. For medical applications, however, these issues present a much greater challenge \u2014 imperfect DNA edits are unacceptable, and efficient delivery of the prime-editing system to cells will be crucial. So although prime editing certainly has the potential to give us unprecedented control over the blueprint of life, only time will tell whether it becomes just another tool in the CRISPR toolbox or a cure-all for genetic diseases.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<div class=\"emphasis\">doi: 10.1038\/d41586-019-03392-9<\/div>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>(\uc6d0\ubb38: <a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03392-9?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29\">\uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h4 class=\"article-item__title serif\">CRISPR: the movie<\/h4>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h5>New gene-editing documentary showcases biology\u2019s hottest tool \u2014 up to the point when things went awry. By Amy Maxmen<\/h5>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<div class=\"article__body serif cleared\">\n<figure class=\"figure\">\n<div class=\"embed intensity--high\">\n<div class=\"embed intensity--high\"><img decoding=\"async\" class=\"figure__image\" src=\"https:\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-03479-3\/d41586-019-03479-3_17295640.jpg\" alt=\"A teenager with sickle-cell disease looks at a tube containing the CRISPR gene editing machinery\" data-src=\"\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-03479-3\/d41586-019-03479-3_17295640.jpg\" \/><\/div>\n<\/div><figcaption>\n<p class=\"figure__caption sans-serif\"><span class=\"mr10\">David Sanchez appears in the documentary: he has sickle-cell anaemia, which could one day be addressed using gene editing.<\/span>Credit: Wonder Collaborative<\/p>\n<\/figcaption><\/figure>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>At the start of\u00a0<i>Human Nature<\/i>, a documentary about the gene-editing tool CRISPR, we meet a young man with sickle-cell anaemia. David Sanchez is wise beyond his years, driving home the injustice of his gruelling blood infusions and shortened lifespan. Researchers are testing a therapy for his condition in clinical trials using CRISPR.<\/p>\n<p>This is a film probing the unknown future of a technology that, within the past decade, has skyrocketed from obscurity to become the subject of a Netflix series called\u00a0<i>Unnatural Selection<\/i>\u00a0that debuted on 18 October (the trailer promises provocation by leading with biohackers injecting the editing tool).\u00a0<i>Human Nature<\/i>\u00a0does not take a shock\u2013horror approach. This is the film that scientists would probably prefer the public to see.<\/p>\n<p>The project began with a meeting between the Wonder Collaborative, a scientific documentary organization based in San Francisco, California, and CRISPR co-discoverer Jennifer Doudna, a biochemist at the University of California, Berkeley (UC Berkeley), and her colleagues. The scientists guided the film-makers, led by a team of co-producers (including former cell biologist Sarah Goodwin and journalists Dan Rather and Elliot Kirschner) and director Adam Bolt, on the scientific and ethical issues. And the film-makers read up on the technology themselves. When the film was nearly complete, they sought feedback from members of the National Academies of Science, Engineering and Medicine.<\/p>\n<p>As a result, the film is high on the thrill and potential of discovery, and every scientist and bioethicist featured is passionate and thoughtful. Notably, the documentary sidesteps academic politics, such as the ongoing patent battle over who will reap CRISPR\u2019s financial rewards. And it lacks input from scientists outside the United States and western Europe \u2014 such as from China, where the first human embryos have been edited \u2014 or from policymakers with the power to restrict what research is permissible. However, it does feature a handful of people who have genetic disorders as well as parents of children with these maladies.<\/p>\n<p>&nbsp;<\/p>\n<figure class=\"figure\">\n<div class=\"embed intensity--high\">\n<div class=\"embed intensity--high\"><img decoding=\"async\" class=\"figure__image\" src=\"https:\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-03479-3\/d41586-019-03479-3_17295650.jpg\" alt=\"Jennifer Doudna in her lab at the Innovative Genomics Institute in Berkeley, California\" data-src=\"\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-03479-3\/d41586-019-03479-3_17295650.jpg\" \/><\/div>\n<\/div><figcaption>\n<p class=\"figure__caption sans-serif\"><span class=\"mr10\">Jennifer Doudna, one of the CRISPR pioneers central to the film.<\/span>Credit: Wonder Collaborative<\/p>\n<\/figcaption><\/figure>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><i>Human Nature<\/i>\u00a0follows a straight path, beginning with the seeds of genetic engineering in the 1960s and ending in the ethical quagmires of making changes to human DNA that future generations could inherit. The film will be educational for people who haven\u2019t heard of CRISPR before; little will be new for those who have. Having covered the story from the beginning, I enjoyed watching the who\u2019s who of CRISPR\u2019s early years speak for themselves.<\/p>\n<p>And the technology itself is covered beautifully. The camera swoops over crystalline salt pools in Spain, where Francisco Mojica, a microbiologist at the University of Alicante, ponders the repeated genetic letters in bacterial genomes \u2014 and the \u2018spacers\u2019 of unidentified DNA sequences in between. In 2005, he revealed that the enigmatic spacers mimic genes from viruses that once infected the microbes, and that these sequences form a kind of \u2018memory\u2019 that allows bacteria to recognize and attack the invaders in future. Animations of double helices clarify what happens; they reappear when Doudna\u2019s team adapts CRISPR as a laboratory workhorse. Even this scene has a pulse, due to the ever-enthusiastic Fyodor Urnov, science director at the Innovative Genomics Institute, UC Berkeley\u2019s centre focused on CRISPR. Together with the enzyme Cas9, CRISPR spots and snips genes that it\u2019s been programmed to find.<\/p>\n<p>Feng Zhang at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, appears briefly. But scant attention is devoted to his groundbreaking studies from 2013 enabling CRISPR to edit animal DNA (these are the experiments at the centre of the Broad\u2019s contested patents). And although a montage of headlines shows a subsequent flurry of experiments in which scientists edit various organisms, little is said about how these studies have pushed forwards fields ranging from evolutionary biology to agriculture. Nor do we learn about scientists\u2019 continuing struggle to insert genes using CRISPR in most organisms other than mice and flies. Their attempts often fail, or result in side effects or death.<\/p>\n<p>The film-makers probably feared that audiences would weary of details. But I was hungry for an update on what scientists are actually doing right now. That\u2019s especially true when it comes to editing people. But rather than dwell on a couple of dozen CRISPR-based therapies in early stages of testing, the film bounds into the possibilities of engineering humans using CRISPR with an ominous clip of Russian president Vladimir Putin speaking in 2017. Soldiers, he says, could be endowed with the ability to fight without pain. And Urnov explains how: CRISPR could be used to delete a gene that transmits pain signals to the brain. He says he\u2019s sure that this will become an analgesic treatment offered to cancer patients in pain.<\/p>\n<p>The rest of the film centres on the ethics of human editing, as if everything were possible. George Daley, a bioethicist at Harvard Medical School in Boston, Massachusetts, draws a line between editing embryos and editing adults; in the former case, children would be born with the alteration in all their cells and changes would be passed down through generations. All the scientists (the protagonists of this film) are conscientious. Doudna, for example, says that Hitler showed up in one of the nightmares she had that were triggered by her anxiety over the potential misuse of the tool. In 2015, Urnov and his colleagues argued that editing embryos, sperm and eggs should be banned for now<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03479-3?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR1\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">1<\/a><\/sup>. And earlier this year, Zhang and others recommended that scientists come up with a framework that governments could use to evaluate research proposals as the science of gene editing progresses<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03479-3?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR2\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">2<\/a><\/sup>.<\/p>\n<p>Still, other scientists can\u2019t contain their excitement. Stephen Hsu, a co-founder of Genomic Prediction, a genetic testing company for in vitro fertilization in North Brunswick, New Jersey, suggests that, eventually, editing could advance humanity by making people healthier, longer-lived or smarter. The documentary pushes him on this point, and flashes a Nazi propaganda clip. Hsu counters that his vision is different from eugenics because the choice to edit is made by parents.<\/p>\n<p>Alta Charo, a bioethicist at the University of Wisconsin\u2013Madison, also dismisses certain fears, pointing out, for example, that characteristics such as intelligence are controlled by multiple genes and by the environment. But she concedes that there is a risk to editing, and therefore it shouldn\u2019t be used frivolously. Just 30 out of 195 countries have banned the editing of human embryos, sperm and eggs in the clinic with CRISPR, and the rules might not govern pure research.<\/p>\n<p><i>Human Nature<\/i>\u00a0traces CRISPR up to a pivotal moment. The film was nearly finished when the news was reported last November that twin girls had been born after Chinese biophysicist He Jiankui had used CRISPR to edit their embryos. So the film-makers just spliced it in as an afterthought. After the heroes of the film had spent so much time expounding on the need to prevent this outcome, its sudden fruition is troubling. Asked why the film-makers didn\u2019t revise the documentary to focus on the case, Kirschner says that they decided there was value in what they had: a film on CRISPR\u2019s origins. Plus, we truly don\u2019t know what will happen next. Kirschner writes: \u201cIt is impossible to tell whether it will ultimately be seen as an inflection point or an aberration.\u201d<\/p>\n<p>The Wonder Collaborative had considered creating just a brief CRISPR explainer. I\u2019m glad they opted for a full-length feature: it gives them time to strike a nerve. For me, this happened in the scenes with Sanchez. At the end of the film, after so many researchers have gushed about the power of CRISPR to cure disease, the interviewer asks Sanchez if he wished his parents had used the tool to prevent his being born with a deadly condition. Sanchez pauses, and says no: \u201cI don\u2019t think I\u2019d be me.\u201d<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<div class=\"emphasis\">doi: 10.1038\/d41586-019-03479-3<\/div>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>(\uc6d0\ubb38: <a href=\"https:\/\/www.nature.com\/articles\/d41586-019-03479-3?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29\">\uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&nbsp; &nbsp; The ultimate goal of genome editing is to be able to make any specific change to the blueprint of life. A \u2018search-and-replace\u2019 method<a href=\"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4845\" class=\"more-link\">(more&#8230;)<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[33,34,29],"tags":[],"class_list":["post-4845","post","type-post","status-publish","format-standard","hentry","category-do-biology","category-lets-do-chemistry","category-lets-do-science"],"aioseo_notices":[],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack-related-posts":[{"id":2952,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2952","url_meta":{"origin":4845,"position":0},"title":"The CRISPR \ufefffix that could combat inherited blood disorders","author":"biochemistry","date":"March 27, 2019","format":false,"excerpt":"\u00a0 Researchers have finally identified a reliable way to edit the genes of blood stem cells. \u00a0 The elongated red blood cells of people with sickle-cell disease can block small blood vessels, reducing the flow of oxygen to nearby tissues. Credit: Eye of Science\/SPL \u00a0 \u00a0 \u00a0 An enhanced version\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3891,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3891","url_meta":{"origin":4845,"position":1},"title":"Inserting DNA with CRISPR","author":"biochemistry","date":"July 16, 2019","format":false,"excerpt":"\u00a0 \u00a0 Most prokaryotes rely on the CRISPR-Cas system for adaptive immunity against viruses and mobile elements (1,\u00a02). Small RNAs produced from CRISPR direct Cas effector proteins to seek and destroy nucleic acids from invaders that have complementary target sites (3). There are multiple types of CRISPR, which are defined\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3361,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3361","url_meta":{"origin":4845,"position":2},"title":"When genome editing goes off-target","author":"biochemistry","date":"April 19, 2019","format":false,"excerpt":"\u00a0 \u00a0 Editing DNA in eukaryotic cells with CRISPR-based systems has revolutionized the genome engineering field. Cas (CRISPR-associated) endonucleases are directed to a particular location in the genome by a short guide RNA, providing an easily programmable strategy to target any section of DNA. As of now, two CRISPR-based approaches\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3988,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3988","url_meta":{"origin":4845,"position":3},"title":"The long shadow of a CRISPR scandal","author":"biochemistry","date":"August 3, 2019","format":false,"excerpt":"\u00a0 He Jiankui's controversial gene-editing experiment brought intense scrutiny to CRISPR scientists in China, and they're outraged. \u00a0 As He Jiankui strode to the podium at last year's summit on human genome editing in Hong Kong, China, more than 1 million people watched online. PHOTO: ANTHONY WALLACE\/AFP\/GETTY IMAGES \u00a0 \u00a0\u2026","rel":"","context":"In &quot;Essays on Science&quot;","block_context":{"text":"Essays on Science","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=32"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2540,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2540","url_meta":{"origin":4845,"position":4},"title":"Precision CRISPR editing","author":"biochemistry","date":"January 18, 2019","format":false,"excerpt":"\u00a0 \u00a0 The most popular gene-editing tool, CRISPR-Cas9, generates breaks in the genome that are subsequently repaired by a mix of cellular pathways. Yet, the repair outcomes are not random. Using machine-learning algorithms to analyze large amounts of Cas9-mediated, genome-wide editing events in a range of cells, Shen\u00a0et al., Allen\u00a0et\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3409,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3409","url_meta":{"origin":4845,"position":5},"title":"CRISPR gene-editing creates wave of exotic model organisms","author":"biochemistry","date":"April 23, 2019","format":false,"excerpt":"\u00a0 But the practical challenges of breeding and maintaining unconventional lab animals persist. \u00a0 The Hawaiian bobtail squid (Euprymna scolopes) alters the camouflage patterns on its skin based on what it sees.Credit: Eric Roettinger\/Kahi Kai Images \u00a0 \u00a0 Joseph Parker has wanted to know what makes rove beetles tick since\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]}],"jetpack_sharing_enabled":false,"jetpack_shortlink":"https:\/\/wp.me\/p9Xo1j-1g9","_links":{"self":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/4845","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=4845"}],"version-history":[{"count":3,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/4845\/revisions"}],"predecessor-version":[{"id":4848,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/4845\/revisions\/4848"}],"wp:attachment":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4845"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=4845"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=4845"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}