CRISPR nanotech 'gene editing' for good or ill?

[TonyGosling]

A woman, her discovery and how she changed the world
Emmanuelle Charpentier has given biologists a new tool: "Crispr" allows genes to be changed amazingly precisely and safely. Doctors want to use it to cure AIDS, cancer and hereditary diseases. Will man soon take evolution into his own hands?
By Max Rauner and Martin Spiewak
June 27, 2016 DIE ZEIT No. 27/2016, June 23, 2016 168 comments
Emmanuelle Charpentier: The illustration shows Emmanuelle Charpentier (left), discoverer of gene surgery Crispr. Thanks to her, people who, like Gavriel (right), have an inherited disease may be cured in the future.
The illustration shows Emmanuelle Charpentier (left), discoverer of gene surgery Crispr. Thanks to her, people who, like Gavriel (right), have an inherited disease may be cured in the future.

[TonyGosling]

Potential DNA Damage from CRISPR “Seriously Underestimated,” Study Finds
A flurry of recent findings highlight a contentious question in this area
https://www.scientificamerican.com/article/potential-dna-damage-from-c rispr-seriously-underestimated-study-finds/

By Sharon Begley, STAT on July 16, 2018
Potential DNA Damage from CRISPR "Seriously Underestimated," Study Finds
Credit: Getty Images
From the earliest days of the CRISPR-Cas9 era, scientists have known that the first step in how it edits genomes—snipping DNA—creates an unholy mess: Cellular repairmen frantically try to fix the cuts by throwing random chunks of DNA into the breach and deleting other random bits. Research published on Monday suggests that’s only the tip of a Titanic-sized iceberg: CRISPR-Cas9 can cause significantly greater genetic havoc than experts thought, the study concludes, perhaps enough to threaten the health of patients who would one day receive CRISPR-based therapy.

The results come hard on the heels of two studies that identified a related issue: Some CRISPR’d cells might be missing a key anti-cancer mechanism and therefore be able to initiate tumors.

The DNA damage found in the new study included deletions of thousands of DNA bases, including at spots far from the edit. Some of the deletions can silence genes that should be active and activate genes that should be silent, including cancer-causing genes.


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Leading CRISPR companies scrambled to play down the latest threat to what they hope will be a multibillion-dollar business—and to their stock prices, but investors reacted with alarm. Within the first 20 minutes of when the study was released, the three publicly traded CRISPR companies lost more than $300 million in value.

The companies questioned whether the CRISPR-caused DNA damage reported in the new study applied to the kind of cells they’re planning to CRISPR. They emphasized that if genomic scrambling is at all common then it should also be seen in earlier forms of genome-editing such as zinc fingers and TALENs (but apparently isn’t). And they insisted they’re on the case.

“We’re not Pollyannaish about this,” said geneticist Tom Barnes, chief innovation officer at Intellia Therapeutics. For its mouse experiments, Intellia analyzes edited genomes for collateral damage both near the editing target and tens of thousands of DNA letters away, he said, but “we have not seen any [cancer-causing] transformation of these cells, even with all the edits we’ve introduced.”

In a statement, Editas Medicine spokeswoman Cristi Barnett said the possibility of genetic chaos from CRISPR is “an interesting topic” that the company “actively examine[s].” The reported DNA havoc, she said, is not “specifically problematic in our work to make CRISPR-based medicines.” CRISPR Therapeutics did not respond to requests for comment.

Academic scientists were less dismissive of the new study, in Nature Biotechnology. One leading CRISPR developer called it “well-done and credible,” “a cautionary note to the [genome-editing] community,” and consistent with other research showing that the DNA cuts that CRISPR makes, called double-stranded breaks, “can induce the types of genomic DNA rearrangements and deletions they report.” He asked not to be identified so as not to jeopardize business relationships with genome-editing companies.


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But just as critics of last month’s studies asked why, if CRISPR’d cells can initiate cancer, no CRISPR’d mice had turned up with tumors, so scientists raised similar questions about the new genomic havoc finding: Why don’t scientists see it when they analyze the DNA of CRISPR’d cells?

“You find what you look for,” said Bradley. “No one is looking at the impact [of these DNA changes] on downstream genes.”

And few studies conduct full-out genome sequencing of CRISPR’d cells. Moreover, scientists typically search for one form of the collateral damage the Sanger study found—deletions of thousands of DNA bases (the double helix’s famous A’s, T’s, C’s, and G’s)—using a standard technique called PCR, which makes millions of DNA copies. But to work, PCR must attach to a “binding site” on DNA; CRISPR sometimes deletes that binding site, said Bradley, whose team used a different technique to analyze the double helix for collateral damage from CRISPR.

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The Sanger scientists didn’t set out to find collateral DNA damage from CRISPR. As they investigated how CRISPR might change gene expression, a “weird thing” showed up, Bradley said: The target DNA was accurately changed, but that set off a chain reaction that engulfed genes far from the target. The scientists therefore changed course.

When they aimed CRISPR at different targets in mouse embryonic stem cells, mouse blood-making cells, and human retinal cells, “extensive on-target genomic damage [was] a common outcome,” they wrote in their paper. In one case, genomes in about two-thirds of the CRISPR’d cells showed the expected small-scale inadvertent havoc, but 21 percent had DNA deletions of more than 250 bases and up to 6,000 bases long.


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Since therapeutic uses of CRISPR would edit the genomes of billions of cells in, say, a patient’s liver, even rare DNA damage “makes it likely that one or more edited cells… would be endowed with an important [disease-causing] lesion,” the scientists wrote.

Nature Biotechnology took a year to publish the paper, after asking Bradley numerous variations of “are you sure?” and “did you consider this?” and asking him to run additional experiments, Bradley said. The results all held up.

The one U.S. clinical trial using CRISPR’d cells began recruiting patients this year. It will use CRISPR to make immune cells, removed from patients with any of four types of cancer, attack telltale molecules on the tumor cells’ surface. Asked what genome analysis he plans to do, lead investigator Dr. Edward Stadtmauer of the University of Pennsylvania said, “We are doing extensive testing of the final cellular product as well as the cells within the patient.”

The possibility of adverse consequences from CRISPR’d cells has caused some company officials to argue that if, say, their therapy cures a child of a devastating disease, but increases her risk of cancer, that might be an acceptable trade-off.

That argument may well prevail. In 2003, however, when a boy in a gene therapy trial in France developed leukemia because the repair gene landed in the wrong place in his genome and activated a cancer-causing gene, it shut down gene therapy development on both sides of the Atlantic for years.

[TonyGosling]

Whitney Webb: Want Some CRISPR In Your Body? Bill Gates Partners With DARPA & Department of Defense For New DNA Nanotech COVID19 Vaccine?

Link


Whitney Webb: Want Some CRISPR In Your Body? Bill Gates Partners With DARPA & Department of Defense For New DNA Nanotech COVID19 Vaccine?
https://www.youtube.com/watch?v=2MGXePjIzXE

[TonyGosling]

The CRISPR Baby Scandal Gets Worse by the Day
The alleged creation of the world's first gene-edited infants was full of technical errors and ethical blunders. Here are the 15 most damning details.
https://www.theatlantic.com/science/archive/2018/12/15-worrying-things -about-crispr-babies-scandal/577234/

ED YONG DECEMBER 3, 2018

He Jiankui attends the International Summit on Human Genome Editing at the University of Hong Kong.REUTERS
Link Copied Updated on December 4 at 10:55 a.m. ET.

Before last week, few people had heard the name He Jiankui. But on November 25, the young Chinese researcher became the center of a global firestorm when it emerged that he had allegedly made the first crispr-edited babies, twin girls named Lulu and Nana. Antonio Regalado broke the story for MIT Technology Review, and He himself described the experiment at an international gene-editing summit in Hong Kong. After his talk, He revealed that another early pregnancy is under way.

It is still unclear if He did what he claims to have done. Nonetheless, the reaction was swift and negative. The crispr pioneer Jennifer Doudna says she was “horrified,” NIH Director Francis Collins said the experiment was “profoundly disturbing,” and even Julian Savulescu, an ethicist who has described gene-editing research as “a moral necessity,” described He’s work as “monstrous.”

Such a strong reaction is understandable, given the many puzzling and worrying details about the experiment. Even without any speculation about designer babies and Gattaca-like futures that may or may not come to pass, the details about what has already transpired are galling enough. If you wanted to create the worst possible scenario for introducing the first gene-edited babies into the world, it is difficult to imagine how you could improve on this 15-part farce.

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The First Man to Have His Genes Edited Inside His Body
SARAH ZHANG
1. He didn’t address an unmet medical need.

He focused on a gene called CCR5, which the HIV virus uses as a doorway for infiltrating human cells. To lock the virus out, several scientists have tried extracting the immune cells of HIV patients and deactivating CCR5 using gene-editing techniques before injecting the cells back into the body. Although Nana and Lulu’s father is HIV-positive, neither of the infants actually had HIV. As I’ve written before, He’s team deactivated a perfectly normal gene in an attempt to reduce the risk of a disease that neither child had—and one that can be controlled through safe-sex education or antiviral drugs. Even if you wanted to block CCR5 specifically, there are drugs out there that could do the job, many of which have been repeatedly tested in clinical trials. The rationale for using a method as extreme and untested as gene editing doesn’t hold up.

Read: You may already be immune to crispr

Deactivating CCR5 doesn’t confer complete immunity to HIV, either, since some strains of the virus can enter cells via a different protein. And although people with natural deficiencies in the gene appear healthy, they might be more susceptible to West Nile virus, and more likely to die when they catch influenza. Essentially, He gave Nana and Lulu resistance to a virus that they could have avoided in myriad other ways, and may have opened them up to other dangers.

2. The actual editing wasn’t executed well.

He’s data haven’t been published or peer reviewed, so many of the details of his experiment are unclear. But based on the slides that he presented at the Hong Kong summit, other scientists have denounced the work for being amateurish.

For example, it appears that He only managed to edit half of Lulu’s CCR5 genes; the rest are normal. That could either be because every cell in her body has one normal copy of CCR5 and one edited one (she’s heterozygous) or because half of her cells carry two edited genes and half carry two normal ones (she’s mosaic). If it’s the former, she would not be resistant to HIV. If it’s the latter, it depends on whether her immune cells specifically carry the edits. The same might apply to Nana, who, based on the slides, seems to also have normal copies of CCR5 somewhere.

What’s more, the edited cells don’t seem to have been edited in the right way. He planned to delete a small section of the CCR5 gene, mimicking a naturally occurring mutation called delta 32 that’s found in about 10 percent of Europeans. But according to Sean Ryder, a biochemist from the University of Massachusetts Medical School, He’s slides show no sign of delta 32 in either girl. Instead, Lulu has an entirely different CCR5 mutation, and Nana has two. These mutations are in roughly the same part of the gene as delta 32, but “it’s a fairly outrageous assumption that any change to this region would lead to some benefit,” Ryder says. “He made new mutations, and there’s no reason to think that they’d be protective—or even that they’d be safe.”

3. It’s not clear what those new mutations will do.

At least two of the three mutations that He introduced into Nana and Lulu’s genomes are substantial changes that could alter how CCR5 works. Typically, scientists would introduce the same mutations into mice or other lab animals to see what would happen. If they felt reassured enough to move into human patients, they could recruit patients with HIV, take out some immune cells, introduce the new CCR5 mutations, transplant the cells back, and monitor the volunteers to see if they’re healthy. “That could take months or years, but to do anything less would be cutting corners,” Ryder says.

But He appears to have leapfrogged over all of those basic checks and implanted the edited embryos into a woman. “The children are test subjects for variants that haven’t been vetted in animals,” Ryder says. What’s shocking about this “is the blatant disregard of all the rules and conventions we have in place for how one should approach any proposed intervention,” said Leonid Kruglyak, a geneticist at the University of California at Los Angeles, on Twitter.

4. There were problems with informed consent.

It’s not clear if the participants in He’s trial were actually aware of what they were signing up for. He relied on an aids association to reach out to the patients and falsely described his work as an “aids-vaccine development project.” He told delegates at the Hong Kong summit that he personally took the volunteers through the informed-consent process, along with another professor. But taking consent is a specific skill that requires training; He had none.

The consent document that he used describes crispr and gene editing, but it does so in heavily technical language. He has said that his patients were “very well educated” and already knowledgeable about gene-editing technology. But according to a news report from the Chinese magazine Sanlian Life Week (which has since been removed, but not before a digital copy was saved and translated), one of the people who dropped out of the experiment had only a high-school understanding of biology, and only heard the term “gene editing” when news stories about He’s experiment broke. The man claimed that he was not informed about the risks of off-target effects, or about the fact that gene editing was a prohibited and ethically controversial technology.

Also, the consent form “is not a consent form,” says Kelly Hills, a bioethicist at Rogue Bioethics. “It’s a business form, of the kind that a company might use when subcontracting.” For example, the section about possible risks says nothing about any negative consequences of deactivating CCR5, and is instead more focused on absolving He’s team of legal responsibility for problems arising from the procedure. The form also gives He’s team rights to use photos of the babies in magazines, calendars, billboards, propaganda, product packaging, and posters in cars and elevators.

5. He operated under a cloak of secrecy …

By his own admission, He didn’t tell his institution, the Southern University of Science and Technology, about the experiment, and took a stint of unpaid leave in February to begin work in secret. The university plans to launch an investigation into the project, which it called a “serious violation of academic ethics and standards” in a statement.

He also claims that he received ethical approval from Shenzhen Harmonicare Hospital. But in a statement, the hospital says that the Medical Ethics Committee never met to discuss such a project, and that the signatures on He’s approval form “are suspected to have been forged.” Meanwhile, He’s laboratory web page has disappeared, as have statements praising his other work on government sites.

6. … but organized a slick PR campaign.

Given how many people He kept in the dark, it is all the more striking that he was simultaneously organizing a public-relations effort. He engaged the services of an American PR consultant, Ryan Ferrell. He created a set of five YouTube videos describing his actions and the rationale behind them. And all of this while the actual technical details of his work have yet to be released in any official publication.

7. A few people knew about He’s intentions but failed to stop him.

Even though He spoke at scientific conferences about his gene-editing research in other animals, he only discussed his ambitions to edit human embryos with a select few. Those included his former adviser Michael Deem of Rice University, who played an active role in the project and was reportedly present in China when several patients were consented. (Deem holds a small stake in He’s two companies, and is under investigation for his involvement in the matter.)

Other scientists were not supportive. As reported in STAT, He also consulted Mark DeWitt of UC Berkeley, who told him not to go ahead with the project. The Associated Press also reported that He expressed an interest in editing human embryos to his former adviser Stephen Quake from Stanford University, who cautioned him in broad terms to seek ethical advice. This February, He also told Stanford’s Matthew Porteus that he had hospital approval to proceed with his experiment. Porteus told the AP that he was angry at He’s naïveté and recklessness, but after chiding him assumed that he would not go ahead.

Read: Chinese scientists are outraged by reports of gene-edited babies

The chair of the Hong Kong summit, David Baltimore, called the episode “a failure of self-regulation by the scientific community.” Baltimore urged other scientists in the field who learn about experiments like He’s to alert the authorities. But this “See something, say something” approach won’t work, says Hills, the bioethicist. “Would scientists actually recognize a bad actor if one was working with them?” she says. “The answer is no. We simply assume that if someone is a colleague, they have shared values.”

“And who do you say something to?” she adds. “We don’t have an international group that oversees gene editing.” China is unusual in that it actually does have a medical-ethics agency that oversees all medical research in the country, and that Porteus or others could have contacted. The United States does not specifically prohibit the gene-editing work that He did, unless it was federally funded. But Hank Greely, an ethics and law professor at Stanford, notes that the step of implanting the embryos would count as distributing a new drug without FDA approval. That’s a federal crime, Greely notes.

8. He acted in contravention of global consensus.

To the extent that there was any global consensus about using gene-editing technologies on human embryos, it was: Don’t rush into it. That was the feeling in 2015 when the U.S. National Academies of Sciences, Engineering, and Medicine convened an international summit of scientists, ethicists, and others to discuss the topic. And it was the view of a landmark report that the same group published in 2017.

The report did not call for an outright ban on germ-line gene editing—that is, altering the DNA of sperm, eggs, or embryos in ways that could cascade through generations—but said that “there is a need for caution.” It should only be done in clinical trials with “rigorous oversight,” “maximum transparency,” and an “absence of reasonable alternatives,” and only after “much more research to meet appropriate risk/benefit standards” and “broad participation and input by the public.”

He’s work, which was both rushed and cloaked in secrecy, clearly did not fit these criteria. And as reported by Antonio Regalado at MIT Technology Review, He wrote in the ethics proposal that accompanied his experiment that the National Academies in their 2017 report had “for the first time” approved germ-line gene editing in human embryos to treat or prevent serious disease. It’s as if he took the absence of a red light as a green one.

9. He acted in contravention of his own stated ethical views.

In July 2017, He spoke at a conference at Cold Spring Harbor Laboratory. He didn’t mention his plans to edit human embryos, but he brought up the case of Jesse Gelsinger, an American teen who died in a botched gene-therapy trial in 1999. To avoid such deaths, and the chilling effect that they can have on research, He urged scientists to move cautiously before editing the genome of embryos.

He also published a paper in The crispr Journal that lays out ethical principles, such as transparency, that he himself violated. The paper was in the works well before the news of the babies broke, and was published two days afterward. Ryan Ferrell, He’s PR consultant, is one of the co-authors.

10. He sought ethical advice and ignored it.

Sharon Begley at STAT reports that He spoke at length with bioethicists William Hurlbut at Stanford University, as well as his son Benjamin Hurlbut at Arizona State University, neither of whom was aware of He’s plans. The elder Hurlbut spent time telling He about opposition to the instrumental use of human embryos in the United States, and the grounds for believing that human life begins at conception. But despite those discussions, He proceeded with his experiments and seems, by Hills’s reading, to have “developed his own personal code that reads like what you would expect from a freshman in the first weeks of Bioethics 101.” *

11. There is no way to tell whether He’s work did any good.

Both Nana and Lulu will be monitored at least until they turn 18. But “the children were already at virtually no risk of contracting HIV,” said Alta Charo, a bioethicist from the University of Wisconsin at Madison, in a statement. This means that “there is no way to evaluate if this indeed conferred any benefit. If they remain HIV-negative, there is no way to show it has anything to do with the editing.”

At the Hong Kong summit, He was asked whether the two children would be treated differently by their parents, who will know that they have been edited. “I don’t know how to answer this question,” He said.

12. He has doubled down.

If He shows any contrition about how these events have unfolded, it has not been obvious. Speaking at the Hong Kong summit, he apologized, but only because news about his work “leaked unexpectedly” before he could present it in a scientific venue. That, He said, took away from the community. Regarding the experiment itself, he said: “I feel proud.”

13. Scientific academies have prevaricated.

In the wake of He’s bombshell, several scientists, including the crispr pioneer Feng Zhang and the stem-cell biologist Paul Knoepfler, have called for a temporary moratorium on similar experiments. By contrast, after the news first broke, the organizing committee of the Hong Kong summit, which includes representatives from scientific academies in Hong Kong, the United Kingdom, and the United States, released a bland statement in which it simply restated the conclusions from its earlier report. A second statement, released after the summit, was stronger, calling He’s claims “deeply disturbing” and his work “irresponsible.”

Read: A reckless and needless use of gene editing on human embryos

But the second statement still discusses the creation of more gene-edited babies as a goal that should be worked toward. The risks are “too great to permit clinical trials of germ-line editing at this time,” it says, but “it is time to define a rigorous, responsible translational pathway toward such trials.” George Daley from Harvard Medical School, who was one of the meeting’s co-organizers, made similar points during the event itself. Given that the world is still grappling with the implications of what has happened, “no, it’s not time yet and it’s tone-deaf to say so,” says Hank Greely.

“Although the chair opened the summit by invoking Huxley’s Brave New World, few of the discussions at the meeting, and nothing in the concluding statement, suggest a meaningful engagement with social consequences,” says the Center for Genetics in Society, a watchdog group.

14. A leading geneticist came to He’s defense.

In an interview with Science, George Church, a respected figure from Harvard and a crispr pioneer, said that he felt “an obligation to be balanced about” the He affair. Church suggested that the man was being bullied and that the “most serious thing” about his experiment was “that he didn’t do the paperwork right.” “[Church’s] comments are incredibly irresponsible,” says Alexis Carere, who is president-elect of the Canadian Association of Genetic Counsellors. “If someone contravenes the rules that we have laid down, we are very justified in speaking out about it. The unfortunate effect of this is that it makes it seem like there is some kind of balance, and George is just in the middle. There is not.”

Carere was also dismayed at the rest of the interview Church gave, where “every sentence was a new ethical maxim that I had never heard of,” she says. For example, Church noted that “as long as these are normal, healthy kids it’s going to be fine for the field and the family.” But unethical actions are still unethical, even if nothing goes wrong. Arguing otherwise gives a pass to scientists who blow past ethical norms, provided that they find something interesting. “It’s bizarro-land consequentialist ethics,” Carere says.

15. This could easily happen again.

Last year, the world learned that a group of scientists had resurrected a virus called horsepox. Several researchers and ethicists criticized that work, arguing that it would make it easier for others to recreate the related (and far more dangerous) smallpox virus. As I wrote in October, regardless of the risks or merits of the experiment, it reveals a vulnerability at the heart of modern science. That is: Small groups of researchers can make virtually unilateral decisions about experiments that have potentially global consequences, and that everyone else only learns about after the fact.

He Jiankui’s experiment reveals that vulnerability in the starkest-possible light.

[TonyGosling]

Fighting the coronavirus outbreak with genetic sequencing, CRISPR and synthetic biology
Kostas Vavitsas | March 10, 2020
https://geneticliteracyproject.org/2020/03/10/fighting-the-coronavirus -outbreak-with-genetic-sequencing-crispr-and-synthetic-biology/

The rapid and frightening spread of the coronavirus has sparked a battle that’s drawing on a host of emerging technologies. Government, industry and academic researchers are scrambling to improve our ability to diagnose, treat and contain a virus that’s threatening to reach pandemic status.

This isn’t the first time researchers have faced off against a dangerous member of this family of viruses. But it is the first time they’ve done it with a toolbox that includes the gene-editing tool CRISPR and the emerging field of synthetic biology.

Indeed, we’ve known about coronaviruses for nearly 60 years. But for several decades, they attracted little attention, causing symptoms similar to the common cold.

That changed in 2003, when a deadly member of the coronavirus family, SARS-COV, spread to 29 countries, killing 774 people. Suddenly, a coronavirus found previously in animals had managed to jump to humans, where it killed nearly 10 percent of those infected. The virus sparked fear across the globe, but was brought under control within a year. Only a small number of cases have been reported since 2004.

Then in 2012 came MERS-COV. The virus emerged in Saudi Arabia, jumping from camels to humans. The virus has never caused a sustained outbreak, but with a mortality rate of 35 percent, it has killed 858 people so far. Infections have been reported in 27 countries, with most in the Middle East. The virus is considered by the World Health Organization to be a potential epidemic threat.

Interestingly, neither of these previous coronavirus threats were stopped by a cure or a vaccine. MERS still lurks in the background, while SARS was contained by what amounts to old-school practices, according to a 2007 article in Harvard Magazine:

Ironically, in this age of high-tech medicine, the virus was eventually brought under control by public-health measures typically associated with the nineteenth century—isolation of SARS patients themselves and quarantine of all their known and suspected contacts—rather than a vaccine.


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Is a cure on the way?
There currently is no cure for this new wave of coronavirus infections (the resulting disease is called Covid-19), even though some antiviral therapies are being tested — and one experimental vaccine is ready for testing in humans. The virus genome has been sequenced and its genetic code may shed light on how the disease starts and spreads, as well as inform on potential pharmaceutical targets for drug development. The Covid-19 virus similarity to the SARS-COV may mean that cures developed for one strain may prove effective for the other. The Canadian company AbCellera plans to test its antibody technology, already tried against MERS-COV, to neutralize the Covid-19 viral bodies.

What is really encouraging is the level of international collaboration aimed to fight this health emergency. Funding bodies, scientific societies and scientific journals have signed a joint statement, agreeing to openly share research findings with the global research community as soon as they are available. The very quick information dissemination gave scientists around the globe several RNA sequences of the virus genome. And these sequences can be used to better understand the epidemiology and origins of the virus. Moreover, the advancements in DNA technology let research groups in academia and industry synthesize the viral genetic material to use in the two areas of focus: detection of virus and vaccine development.


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Early Detection
One of the trickiest things about the coronavirus is its speculated transmission by asymptomatic patients. This increases the number of infections and makes containment measures less effective, spreading fears that the virus may establish a permanent presence in some areas. There are also fears that many incidents lie undetected, spreading the virus under the radar. As of March 9, the virus has infected more than 110,000 people, killing nearly 4,000, in 97 countries.

Several biotech companies have scrambled to provide kits and resources for early and reliable detection of the new coronavirus. Mammoth Bioscience, a San Francisco-based startup, is already working on a detection assay using their CRISPR technology. The DNA technology companies IDT and Genscript already distribute PCR-based kits for detection for research purposes. The Chinese companies BGI and Liferiver Biotech use the same PCR technology for the kits they provide to their countries health authorities.


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Related article: Facing the coronavirus and uncertainty: Why do some of us shrug it off, while others hoard toilet paper?
The French-British biotech Novacyt announced the launch of a diagnostic kit for clinical use in middle February. The kit will also use quantitative-PCR, developed by their sister company Primerdesign. Its high specificity will reduce the analysis time to less than two hours. The company’s CEO Graham Mullis told Reuters that each kit will cost around $6.50, and that they have already received more than 33,000 orders.


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There are 3 variations of our new nCoV-2019 kit, both our standard and advanced are open platform and can be used with any qPCR instrument and our easy kit is compatible with our q16 instrument.#COVID-19 #coronavirus #WHO @PrimerdesignLtd

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Vaccination to halt the disease from spreading
The only way to effectively control and even eliminate the outbreak is to develop a vaccine. Unfortunately, the new outbreak hasn’t attracted the attention of the lead vaccine manufacturers. Non-profit organizations, such as the Coalition for Epidemic Preparedness Innovations (CEPI), have jumped in to fill the gap. But despite the emergency, a vaccine may be several years away from being available

The University of Queensland in Brisbane, Australia, announced that they’re working on a coronavirus vaccine which they hope to have ready within the next few months. The “molecular clamp” approach the Australian researchers have developed is designed to boost the immune system response and work against several viral infections. GlaxoSmithKline has offered its adjuvant technology – adjuvants are added to vaccines to boost their efficiency – to speed up the process.


The Cambridge, MA-based Moderna uses a different approach to make vaccines. Their mRNA technology is modular and very adaptable to use for a new disease or when the epitope (the vaccine’s target) mutates. The company says its vaccine is ready for human trials.

Situation is concerning, but humanity is not at risk
The Covid-19 outbreak has rightly gained the attention of health authorities and the media. If the virus were to reach countries with weaker healthcare systems than China’s, the number of deaths will rise significantly and containment will be even harder. Moreover, the long incubation time of the disease, combined with the asymptomatic spread, make quarantine and isolation measures less effective. The biggest risk is for the new coronavirus to become endemic in certain areas, where the disease is never truly extinct and displays seasonal outbreaks. We don’t want the Covid-19 to become a new flu.

The health authorities of 2020, the biotech industry, and the society in general are better prepared for a coronavirus outbreak than a few years ago. The situation is less risky than MERS and SARS, though the new virus is harder to contain. This outbreak offers a chance for everyone to become more aware of viral infections, the appropriate precautions and get vaccinated according to the official recommendations. And keep in mind that the best way to stay informed is through official sources, such as the WHO and the CDC.

As for the biotech industry, are they playing their part? The answer is a partial yes; there are several companies that immediately scrambled to help the situation. But the big players within the field could be doing more.

Kostas Vavitsas, PhD, is a Senior Research Associate at the University of Athens, Greece. He is also a steering committee member of EUSynBioS. Follow him on Twitter @konvavitsas

The GLP featured this article to reflect the diversity of news, opinion and analysis. The viewpoint is the author’s own. The GLP’s goal is to stimulate constructive discourse on challenging science issues.

[TonyGosling]

New genetic method of using CRISPR to eliminate COVID-19 virus genomes in cells
https://bioengineering.stanford.edu/new-genetic-method-using-crispr-el iminate-covid-19-virus-genomes-cells

There is currently no vaccine or cure towards COVID-19. It is predicted the development of a safe and effective vaccine to prevent COVID-19 will take 12 to 18 months, by which time hundreds of thousands to millions of people may have been infected. With a rapidly growing number of cases and deaths around the world, this emerging threat requires a nimble and targeted means of protection.

Could CRISPR be the next virus killer?
To address this global pandemic challenge, we are developing a genetic vaccine that can be used rapidly in healthy and patients to greatly reduce the coronavirus spreading. We developed a safe and effective CRISPR system to precisely target, cut and destroy COVID-19 virus and its genome, which stops coronavirus from infecting the human lung.

We’ve shown that the CRISPR system can reduce 90% of coronavirus load in human cells. It can also protect humans against essentially 90% of all current and emerging coronaviruses. The project is ongoing, and we are working around the clock towards getting an actual product by combing our CRISPR method with an inhaler-based delivery device.

The project will likely to result in a potential therapeutics towards COVID-19 soon, which can help slow down or eliminate the outbreak.

Relevant Publications or More Information
• A preprint of the work (not yet peer reviewed) can be found here: https://www.biorxiv.org/content/10.1101/2020.03.13.991307v1
• Recent feature in WIRED magazine: https://www.wired.com/story/could-crispr-be-the-next-virus-killer/

Collaborators:
• Stanley Qi (Bioengineering)
• David Lewis (Pediatrics-Immunology)
• Jennifer Cochran (Bioengineering)
• Drew Endy (Bioengineering)

[TonyGosling]

Gene therapy start-up clinches deal of over $1.2b with global pharmaceutical giant
https://www.straitstimes.com/singapore/gene-therapy-start-up-clinches- deal-of-over-12b-with-global-pharmaceutical-giant

Carmine Therapeutics inked the deal with Takeda Pharmaceutical Company on June 19.
Carmine Therapeutics inked the deal with Takeda Pharmaceutical Company on June 19.ST PHOTO: TIMOTHY DAVID
PUBLISHED2 MIN AGOUPDATED2 MIN AGO
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Shabana Begum
SINGAPORE - A local gene therapy start-up has clinched a deal of more than $1.2 billion with a global pharmaceutical giant to develop and eventually commercialise its treatments for rare genetic diseases.

Carmine Therapeutics, formed last year and believed to be the first gene therapy company in South-east Asia, and Takeda Pharmaceutical Company, an R&D-driven, Japanese multinational pharmaceutical company, inked the deal on June 19.

Gene therapy is a treatment where genes are injected into patients to fight or prevent diseases, instead of using chemical drugs or surgery.

Carmine developed a novel technology that uses tiny particles released by red blood cells, called extracellular vesicles, to deliver genes to parts of the body that need to be treated.

Carmine is unable to reveal the rare genetic diseases they are working on at this point.

Once the particles reach the diseased cells or tissues, the genes help them build therapeutic proteins to restore the tissues' normal functions .

Carmine is believed to be the first company in the world to harness red blood cell extracellular vesicles as vehicles for gene therapy.

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Most gene therapy treatments use viruses to deliver genes, but that is undesirable because some patients may develop adverse immune responses to the viruses or reject them, said Carmine's founding vice-president, Dr Ronne Yeo.

In Carmine's therapy, only red blood cells from O Negative blood in blood banks are used because it has the lowest risk of causing adverse reactions to patients, he added.


A computer-generated illustration of the cross-section of an extracellular vesicle. PHOTO: CARMINE THERAPEUTICS
Additionally, the vesicles from red blood cells are also able to pack larger genes compared to viruses, are cheaper to manufacture, and can access more organs than other vehicles.

The vesicles' ability to hold and deliver genes and their advantages over viral vehicles were discovered by two Singaporean researchers, Dr Minh Le and Dr Shi Jiahai, both scientific co-founders of Carmine.

Their findings were published in scientific journal Nature Communications in 2018.

The start-up is also believed to be the first gene therapy company in Asia to use non-viral vehicles.

Carmine's technology is called Red Cell EV Gene Therapy (Regent), where EV stands for extracellular vesicles.

"Developing alternative gene therapy delivery vehicles like the Regent platform that could address the challenges of (virus-based) gene therapy is critical to one day delivering next-generation cures for rare diseases," said Takeda Rare Diseases Drug Discovery Unit head Madhu Natarajan.

Carmine is based in Singapore and Boston, Massachusetts, which is a global hub of biotech.

Since it was formed last year, Carmine has been further developing the vesicles, engineering them to tackle different rare genetic diseases, and conducting pre-clinical studies. The company is also aiming to treat cancers with gene therapy in the future.

Mr Lin Xiangqian, Carmine's founding chief executive, said Takeda's funding and collaboration will help the start-up further optimise its technology and accelerate it towards clinical trials and commercialisation of the treatments.

"We are working very hard for patients with rare genetic diseases, and we are working to put locally developed biotech inventions on the world map," he added.