\u201cIf CRISPR realises 10 per cent of what we practitioners of gene editing dream it to be able to do, it will rival the greatest advances in the history of biomedicine as a technology to impact public health.\u201d<\/p>\n
Urnov is talking via a crackly Zoom link from his office at the Innovative Genomics Institute (IGI) in Berkeley, California, which is at the forefront of what may prove to be the defining scientific breakthrough of the 21st Century.<\/p>\n
CRISPR is a genome editing technology that allows scientists to cut DNA with incredible precision and insert or delete DNA to correct unwanted mutations. To oversimplify the technology, it\u2019s the power to edit the building blocks of life, just like text on a computer screen. Not only could it enable scientists to switch off genes that lead to a broad spectrum of disease, but it will unshackle all of us from the genetics we\u2019re born with.<\/p>\n
\u201cThe knowledge gained is amazing and it\u2019s just really accelerated basic research. That in itself is already transformative,\u201d says Dr Robin Lovell-Badge<\/a>, from the Crick Institute. \u201cAnd the notion that we can actually treat people with genetic diseases in a way that was never possible before is mind boggling.\u201d<\/p>\n For much of the past decade, the technology has been confined to the lab. Now, though, the first CRISPR therapies are changing the fate of people born with debilitating inherited conditions. Most of us haven\u2019t realised it yet, but we\u2019re in the foothills of a profound medical and technological revolution that raises not only the prospect of new treatments and cures, but also huge questions about ethics, equality and health justice.<\/p>\n The incoming wave of gene-editing applications has been compared to the Industrial Revolution or the birth of the internet in terms of the game-changing impact it will have on society.<\/p>\n Biochemist Dr Jennifer Doudna<\/a> established the IGI to tackle all of that and more. As a non-profit organisation, the institute exists not just to research gene editing, but also make it affordable and accessible to everyone. It\u2019s a big claim, given the breadth of CRISPR\u2019s potential, so the IGI\u2019s leadership team agreed to give BBC Science Focus<\/em> an exclusive overview of its efforts.<\/p>\n It was there on the Berkeley campus where Doudna and Dr Emmanuelle Charpentier<\/a> changed the world nearly a decade ago. Their collaboration led to the development of CRISPR-Cas9, the gene-editing tool described in a landmark 2012 paper that won a Nobel Prize.<\/p>\n \u201cI think we both had a little sense of, you know, kind of a chill,\u201d she says. \u201cI still remember that feeling of hairs standing up on my neck, thinking there\u2019s something really interesting here. And I would wager that neither of us at the time had any idea where it would end up, because I don\u2019t think one ever does.\u201d<\/p>\n CRISPR isn\u2019t the only gene-editing technology, and the IGI is not the only institute pioneering the field of study. But CRISPR is more versatile, easier to use and cheaper than a lot of other technologies. And what\u2019s astonishing is the speed of progress. In less than a decade it\u2019s gone from discovery to human trials and potential cures, something that\u2019s practically unheard of in biomedicine.<\/p>\n \u201cIt\u2019s a little bit of whiplash,\u201d says Dr Brad Ringeisen<\/a>, executive director of the IGI. \u201cThink about nanoparticles, the nano revolution. Pfizer has nanoparticles in their COVID mRNA vaccine<\/a>, but that [technology] has taken 30 or 40 years.\u201d<\/p>\n Read more about CRISPR:<\/strong><\/p>\n People born with sickle cell disease will be among the first to benefit from advances in gene editing. In 2019, a woman called Victoria Gray became one of the first people in the world to be treated for a genetically inherited disease with a CRISPR-based therapy.<\/p>\n Born with sickle cell anaemia, she required strong pain medication and regular blood transfusions to stave off the effects of the mutated gene that makes red blood cells warp and block the flow of blood and oxygen around the body. Aside from bouts of excruciating pain, sickle cell anaemia can lead to stroke, hypertension, organ damage and more.<\/p>\n The treatment was not simple. Doctors removed bone marrow cells from Gray and the other patients in the trial, then used CRISPR to edit a gene that activates production of foetal haemoglobin, a protein that can alleviate the symptoms of sickle cell disease. The patients then underwent chemotherapy to destroy most of their bone marrow, after which billions of edited cells were infused back into their bodies.<\/p>\n Gray no longer requires medication or transfusions, and neither do the other people in her trial, which included patients with a related blood disorder. It seems that a one-time CRISPR treatment has cured them.<\/p>\n \u201cSickle cell disease is probably the easiest target that affects the most people,\u201d says Ringeisen. \u201cIt\u2019s about as simple as you can possibly get: you go in and either turn on an alternative gene or you try to correct the one thing. One hundred thousand people in United States have sickle cell disease and I think it\u2019s over a million people worldwide. So there\u2019s a huge impact that can be had.\u201d<\/p>\n The IGI is preparing its own sickle cell trial, but the institute\u2019s scope also includes many other conditions. As well as blood disorders, it has active research projects on autoimmune disease, neurological disease, cancer and COVID-19. One promising avenue of research is with T-cells, sometimes described as the troops on the ground of our immune system.<\/p>\n Dr Alex Marson<\/a>, the IGI\u2019s director of human health, is running a lab that is working to engineer T-cells using CRISPR to treat different kinds of disease. He is currently planning a clinical trial with a family where a strong genetic mutation has caused different manifestations of autoimmune disease in the younger generation.<\/p>\n \u201cIn the lab we\u2019ve corrected cells from these children,\u201d he says. \u201cNow we\u2019re working towards doing a clinical trial to take those gene-corrected T-cells and infuse them into at least one of these young adults to try to restore balance in the system and treat the autoimmune disease.\u201d<\/p>\n Whereas current T-cell therapies are wildly expensive, Marson envisions a future where off-the-shelf T-cells are manufactured to treat different kinds of disease, their production industrialised to a scale that makes them accessible to anybody who needs them.<\/p>\n \u201cWe can treat infectious diseases by designing immune cells that recognise infections,\u201d he says. \u201cI think we\u2019re going to have this sort of flexible ability to actually write the language of the DNA in the immune cell and use it in a drug platform.\u201d<\/p>\n This is where things start getting really interesting, because it showcases just how broad the medical applications of CRISPR will be. Its potential lies not just in those conditions caused by a single genetic mutation like sickle cell disease, but any disease that has a genetic component, either in terms of susceptibility or protection.<\/p>\n That includes many of the major killers, including cancer, cardiovascular disease and neurodegenerative disease, plus chronic conditions like inflammatory bowel disease and rheumatoid arthritis.<\/p>\n \u201cAll disease is on the map,\u201d says Ringeisen.<\/p>\n Part of what gives scientists optimism is that gene editing can be used to bestow protective DNA on a person as well as correcting unwanted mutations.<\/p>\n \u201cWe know there is a genetic change you can make that will dramatically lower your risk of heart disease,\u201d says Urnov. \u201cHow do we know that? Because of very rare individuals who have those genetic changes. And when you study lots of them, it\u2019s kind of jaw-dropping. I\u2019m not going to say they\u2019re immune to heart disease, but they\u2019re close to it.\u201d<\/p>\n Doudna believes that CRISPR could even be used more to prevent disease than to treat it. \u201cImagine a time when people get their genome sequenced and be told that you have a gene that makes you have a higher likelihood of getting cardiovascular disease,\u201d she says. \u201cBut you have the option of editing your cells so that you don\u2019t have to wait to find out if you\u2019re one of the unlucky folks that is susceptible.\u201d<\/p>\n Today, lots of us take preventative action to protect our future health. It could be anything from eating a high-fibre diet to keep heart disease at bay, to having a double mastectomy because breast cancer runs in the family. Would you be comfortable editing your DNA to achieve the same results?<\/p>\n It\u2019s harder to do the cost-benefit analysis when you\u2019re talking about such experimental therapies. There are some who will say that any form of gene editing is \u2018playing God\u2019 and conspiracy theories around COVID-19 vaccines show how mistrust in new technologies can spread.<\/p>\n \u201cThere can be misrepresentations or just misconceptions embedded in the public mindset that can have a negative effect on what I think should be positive advances,\u201d Doudna says. \u201cAnother example of that is the whole anti-GMO movement.\u201d<\/p>\n In November 2018, twin girls were born in China, the so-called CRISPR babies. Biophysicist Dr He Jiankui announced that he had created the world\u2019s first genome-edited babies<\/a> to widespread condemnation.<\/p>\n He engineered mutations in human embryos that were later implanted into a woman, crossing an ethical boundary by altering the human germline, meaning the edits he made would also be passed on to future generations. Additionally, he was criticised for flouting normal safety procedures.<\/p>\n Jiankui claimed that he had disabled a gene called CCR5, offering protection against HIV. His critics pointed out that he could have also inadvertently caused mutations in other parts of the genome. Jiankui was jailed in China for three years at the beginning of 2020 and ordered to pay a three million yuan fine (\u00a3240,000 approx), his work a stark warning to everyone in the gene-editing world.<\/p>\n \u201cThis field is experimental and we are one \u2018severe adverse event\u2019 from the entire effort being frozen,\u201d Urnov says. \u201cThe painful thing for me and for tens of thousands of folks like me who have spent 40 years building human genetic engineering to treat disease, you know, this technology\u2019s now tainted with the concept of designer babies.<\/p>\n \u201cWe have 250 million people on planet Earth with genetic disease. We should not be talking about designing anyone. We should be putting all of our attention to the fact that there are hundreds of millions of our fellow human beings that have had their fate handed to them on genetic platter,\u201d he adds.<\/p>\n There are other challenges to overcome, too. One of the major criticisms of Jiankui\u2019s work stems from the fact that gene editing is not yet so precise that scientists have\u00a0absolute faith that any edit only affects the part of the genome being targeted. There can be so-called \u2018off-target\u2019 effects: unintended genetic modification that occurs elsewhere on the target genome. A worst-case scenario in clinical terms might be \u2018genotoxicity\u2019, where an off-target effect causes DNA damage that could lead to cancer.<\/p>\n For this reason, what\u2019s known as the \u2018delivery challenge\u2019 of CRISPR is a major focus of research, both at the IGI and beyond.<\/p>\n \u201cWe can only gain confidence in the safety of these procedures by performing clinical trials,\u201d says Dr Ross Wilson<\/a>, the IGI\u2019s director of therapeutic delivery. \u201cWe are not so hubristic to think that we have the ability to forecast every possible outcome when a new therapeutic procedure is attempted, which is why these trials are being performed methodically and without haste.<\/p>\n \u201cOnce we have confidence that people\u2019s lives are being saved or transformed for the better, without incurring unwanted outcomes, the technology can be moved into other applications, reducing risks of heart disease, for example.\u201d<\/p>\n There are ways to offset this risk of unintended consequences of gene editing. A patient\u2019s own cells can be sent to the lab for \u2018trial editing\u2019, giving an informed look at what is likely to happen inside that patient\u2019s body when they are dosed.<\/p>\n CRISPRoff technology is also under development. This tool allows researchers to target the epigenome, rather than the genome itself. That is, scientists can turn off a particular gene without cutting a strand of DNA by instead targeting the proteins and other molecules that attach themselves to DNA and control when that gene is switched on or off. Because the genome itself is untouched, researchers expect the risk of unwanted effects to be lower.<\/p>\n \u201cThe pandemic taught us that the public has a major craving for things to be declared \u2018safe\u2019 or \u2018unsafe\u2019, but in reality it\u2019s all about the balance between risk and benefit,\u201d says Wilson. \u201cThat ratio looks extremely promising for CRISPR technology, and it improves each year, so the future is bright for therapeutic genome editing.\u201d<\/p>\n Doudna\u2019s dream for CRISPR is to make it \u201cthe standard of medical care\u201d. For that to happen, one more thing needs to be addressed, and it\u2019s arguably more complex than any technical hurdle: the cost of treatment.<\/p>\n Gene editing is, or could be, a great leveller in healthcare. But like all experimental treatments, it is research-heavy, labour-intensive and expensive. One of Doudna\u2019s fears is that it will become a boutique technology, available only to those who can afford it. This, she says, would not only exacerbate the health gap that already exists between rich and poor, but also create a new kind of health inequality: a gene gap.<\/p>\n The IGI is a non-profit, funded publicly and via philanthropy. Its staff talk of their work not just in technological terms but societal ones too, focused on how to maximise the reach of the technology.<\/p>\n \u201cIt\u2019s a major problem,\u201d Urnov says. \u201cIn the US, [some of] these medicines are sold for $2m, but European countries have refused to even licence them. You have a surreal situation where parents in Europe, whose children have these severe diseases, start GoFundMe campaigns to be able to pay American prices.<\/p>\n \u201cWe have this gap between the fact that this technology is rapidly expanding in its utility and we are struggling, frankly, with how to make it equitable and affordable.\u201d<\/p>\n Add to that the issue of health justice, the fact that if you\u2019re born with an inherited condition, an affordable cure may be possible if enough people have the same illness. That would make it economically viable for pharmaceutical companies to invest in the research to develop new treatments.<\/p>\n If you\u2019re born with a rare genetic mutation, that may not be possible. \u201cThere is this horrific gap between our ability to read that person\u2019s DNA and say, \u2018Yes, this is the mutation that killed your mom and will kill you, I\u2019m sorry to say\u2019, and actually developing a treatment that would help that person. Developing such personalised cures has essentially no commercial value. Nobody will ever make money,\u201d says Urnov.<\/p>\n Lovell-Badge agrees. \u201cThe cost is a problem for it becoming really useful for public health,\u201d he says. \u201c[We need to] start off from the very beginning thinking, \u2018How can we do this in a way that\u2019s going to be more affordable?\u2019 Then you approach the problem in a different way.\u201d<\/p>\n Unlike so much of the biotech industry, addressing this issue is a cornerstone that the IGI was built on \u2013 not just developing novel treatments, but creating scalable pipelines for discovery, testing and rollout.<\/p>\n \u201cOur mission really has to be ensuring that technology benefits everyone,\u201d Doudna says. \u201cThat was the impetus for the Innovative Genomics Institute in the first place. Many institutes, many companies, many academic labs are now developing gene editing, but not with an eye towards controlling cost and doing the science with a focus on public access to that technology. That\u2019s really our purpose.\u201d<\/p>\n The genetic revolution is coming. After pioneering the technology, Doudna is adamant that when it arrives, it\u2019s available to everybody. As more than one of her colleagues tells us, that\u2019s just in her DNA.<\/p>\n Read more about DNA:<\/strong><\/p>\n By Ian Taylor Published: Wednesday, 10 November 2021 at 12:00 am Scientists are a cautious bunch, fond of a caveat even when describing their own research. \u201cOur favourite expressions are \u2018Yes, but\u2026\u2019 and \u2018On the other hand\u2026\u2019 and \u2018It remains unclear\u2026\u2019\u201d says gene editor Dr Fyodor Urnov. \u201cSo please add all of that to what […]<\/p>\n","protected":false},"author":24,"featured_media":268,"template":"","categories":[1],"acf":{"readingTimeMinutes":"14"},"uagb_featured_image_src":{"full":["https:\/\/c01.purpledshub.com\/uploads\/sites\/42\/2021\/11\/crispr-a-guide-to-the-health-revolution-that-will-define-the-21st-century.jpg",1200,800,false],"thumbnail":["https:\/\/c01.purpledshub.com\/uploads\/sites\/42\/2021\/11\/crispr-a-guide-to-the-health-revolution-that-will-define-the-21st-century-150x150.jpg",150,150,true],"medium":["https:\/\/c01.purpledshub.com\/uploads\/sites\/42\/2021\/11\/crispr-a-guide-to-the-health-revolution-that-will-define-the-21st-century-300x200.jpg",300,200,true],"medium_large":["https:\/\/c01.purpledshub.com\/uploads\/sites\/42\/2021\/11\/crispr-a-guide-to-the-health-revolution-that-will-define-the-21st-century-768x512.jpg",768,512,true],"large":["https:\/\/c01.purpledshub.com\/uploads\/sites\/42\/2021\/11\/crispr-a-guide-to-the-health-revolution-that-will-define-the-21st-century-1024x683.jpg",800,534,true],"1536x1536":["https:\/\/c01.purpledshub.com\/uploads\/sites\/42\/2021\/11\/crispr-a-guide-to-the-health-revolution-that-will-define-the-21st-century.jpg",1200,800,false],"2048x2048":["https:\/\/c01.purpledshub.com\/uploads\/sites\/42\/2021\/11\/crispr-a-guide-to-the-health-revolution-that-will-define-the-21st-century.jpg",1200,800,false]},"uagb_author_info":{"display_name":"importmanagerhub@sprylab.com","author_link":"https:\/\/c01.purpledshub.com\/bbcsciencefocus\/author\/importmanagerhubsprylab-com\/"},"uagb_comment_info":0,"uagb_excerpt":"By Ian Taylor Published: Wednesday, 10 November 2021 at 12:00 am Scientists are a cautious bunch, fond of a caveat even when describing their own research. \u201cOur favourite expressions are \u2018Yes, but\u2026\u2019 and \u2018On the other hand\u2026\u2019 and \u2018It remains unclear\u2026\u2019\u201d says gene editor Dr Fyodor Urnov. \u201cSo please add all of that to what…","_links":{"self":[{"href":"https:\/\/c01.purpledshub.com\/bbcsciencefocus\/wp-json\/wp\/v2\/rss_feed\/267"}],"collection":[{"href":"https:\/\/c01.purpledshub.com\/bbcsciencefocus\/wp-json\/wp\/v2\/rss_feed"}],"about":[{"href":"https:\/\/c01.purpledshub.com\/bbcsciencefocus\/wp-json\/wp\/v2\/types\/rss_feed"}],"author":[{"embeddable":true,"href":"https:\/\/c01.purpledshub.com\/bbcsciencefocus\/wp-json\/wp\/v2\/users\/24"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/c01.purpledshub.com\/bbcsciencefocus\/wp-json\/wp\/v2\/media\/268"}],"wp:attachment":[{"href":"https:\/\/c01.purpledshub.com\/bbcsciencefocus\/wp-json\/wp\/v2\/media?parent=267"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/c01.purpledshub.com\/bbcsciencefocus\/wp-json\/wp\/v2\/categories?post=267"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\""Jennifer\"](\""https:\/\/images.immediate.co.uk\/production\/volatile\/sites\/4\/2021\/09\/Jennifer-Doudna-with-CRISPR-modelimage_hires_172505-crop-165b537.jpg?quality=90&resize=620%2C349"\" "\\"\"Jennifer\\"\/")
<\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/picture><\/div>CRISPR\u2019s first successes<\/h2>\n
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<\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/picture><\/div>![\""A\"](\""https:\/\/images.immediate.co.uk\/production\/volatile\/sites\/4\/2021\/09\/GettyImages-140892339-crop-138fed7.jpg?quality=90&resize=620%2C620"\" "\\"\"Sickle\\"")
<\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/picture><\/div>Disease prevention<\/h2>\n
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<\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/picture><\/div>![\""Emmanuelle\"](\""https:\/\/images.immediate.co.uk\/production\/volatile\/sites\/4\/2021\/09\/Alamy_ERMK9X-crop-cb1e4e8.jpg?quality=90&resize=620%2C409"\" "\\"\"Emmanuelle\\"\/")
<\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/source><\/picture><\/div>Could CRISPR create a health inequality?<\/h2>\n
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