A mildly insane idea for disabling the coronavirus

Colorful blobs cluster together like a bunch of grapes.

Enlarge / Diagram of the structure of the virus’ spike protein. (credit: McLellan Lab, University of Texas at Austin)

When the COVID-19 pandemic was first recognized for the threat that it is, researchers scrambled to find anything that might block the virus’ spread. While vaccines have grabbed much of the attention lately, there was also the hope that we could develop a therapy that would block the worst effects of the virus. Most of these have been extremely practical: identify enzymes that are essential for the virus to replicate, and test drugs that block similar enzymes from other viruses. These drugs are designed to be relatively easy to store and administer and, in some cases, have already been tested for safety in humans, making them reasonable choices for getting something ready for use quickly.

But the tools we’ve developed in biotechnology allow us to do some far less practical things, and a paper released today describes how they can be put to use to inactivate SARS-CoV-2. This is in no way a route to a practical therapy, but it does provide a fantastic window into what we can accomplish by manipulating biology.

Throw it in the trash

The whole effort described in the new paper is focused on a simple idea: if you figure out how to wreck one of the virus’ key proteins, it won’t be able to infect anything. And, conveniently, our cells have a system for destroying proteins, since that’s often a useful thing to do. In some cases, the proteins that are destroyed are damaged; in others, the proteins are made and destroyed at elevated paces to allow the cell to respond to changing conditions rapidly. In a few cases, changes in the environment or the activation of signaling pathways can trigger widespread protein destruction, allowing the cell to quickly alter its behavior.

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#biology, #biotechnology, #coronavirus, #genetic-engineering, #science, #spike-protein, #ubiquitin

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Crispr Gene Editing Can Cause Unwanted Changes in Human Embryos, Study Finds

Instead of addressing genetic mutations, the Crispr machinery prompted cells to lose entire chromosomes.

#cell-journal, #chromosomes, #crispr-dna, #dna-deoxyribonucleic-acid, #ethics-and-official-misconduct, #genetic-engineering, #genetics-and-heredity, #mitalipov-shoukhrat, #nobel-prizes, #your-feed-health, #your-feed-science

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What’s Special About Bat Viruses? What We Don’t Know Could Hurt Us

The immune systems of bats are weird, but we don’t know how weird, how they got that way or enough about other animals.

#bats, #coronavirus-2019-ncov, #genetic-engineering, #national-science-foundation, #research, #science-journal, #viruses, #your-feed-animals, #your-feed-science

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Nobel laureate Jennifer Doudna shares her perspective on COVID-19 and CRISPR

CRISPR co-discoverer Jennifer Doudna was named a Nobel laureate in Chemistry today, sharing the honour with Emmanuelle Charpentier . We had the opportunity to speak to Doudna recently at our TechCrunch Disrupt 2020 event, and she shared her thoughts on CRISPR, and how it can be used to test and potentially treat COVID-19, as well as what it may do for our ability to address future pandemics and healthcare crises.

“It’s really interesting to think about the ability to program CRISPR to be detecting not only the the current coronavirus, but also other viruses,” she explained in the interview in September. “We were already working on a strategy to co-detect influenza and coronavirus, as you know that it’s really important to be able to do that, but also to pivot very quickly to detect new viruses that are emerging. I don’t think any of us think that, you know, viral pandemics are going away – I think this current pandemic is a call to arms, and we have to make sure that scientifically, we’re ready for the next attack by a new virus.”

Much closer to hand, CRISPR has the potential to greatly expand testing capabilities in the near-term, and to do so in ways that could change the pace, frequency and nature of testing. That could translate to very different frontline care and pandemic management, across both healthcare facilities as well as any shared workspaces.

“I think from what I’ve seen that very likely before the end of the year, we’re going to see CRISPR diagnostic tests rolling out,” she said. “Whether they’re in laboratory settings – I think that may be the first format that we see – but also something that we’re working on right now at the Innovative Genomics Institute at Berkeley and UCSF and the Gladstone is a strategy for a point-of-care CRISPR tests, where we have a small device that we envision located in different floors of buildings and institutions and dormitories, where you could do very rapid surveillance-type testing of saliva or swab samples.”

Check out the full interview with Doudna above, which also ranges into the most recent advances in CRISPR science, and where it’s heading next for everything from therapeutics, to crop modification.

#biology, #biotech, #biotechnology, #crispr, #emmanuelle-charpentier, #genetic-engineering, #genomics, #health, #innovative-genomics-institute, #jennifer-doudna, #life-sciences, #nobel-prize, #science, #tc

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Nobel Prize in Chemistry Awarded to 2 Scientists for Work on Genome Editing

Emmanuelle Charpentier and Jennifer A. Doudna developed the Crispr tool, which can change the DNA of animals, plants and microorganisms with high precision.

#chemistry, #genetic-engineering, #medicine-and-health, #nobel-prizes, #your-feed-science

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Scribe Therapeutics launches a platform for engineering CRISPR-based therapeutics

A new company called Scribe Therapeutics founded by two former members of CRISPR pioneer Jennifer Doudna’s UC Berkely genetics lab (alongside Doudna herself) launched on Tuesday, debuting a platform designed specifically to help develop and engineer new thereapeutics based on CRISPR for addressing specific diseases, with permanent treatments in patients.

Doudna is part of the leadership team behind Scribe, but it’s primarily led by CEO and co-founder Benjamin Oakes, along with VP of Platform Brett T. Staahl. Oakes and Staahl shared time at Doudna’s lab, with Oakes as a student while Staahl was a postdoc. Staahl’s interest was specifically in how gene editing, and CRISPR in particular, could be used to help treat Huntington’s disease – while Oakes, who originally set out to be a practicing medical doctor, realized early on he actually wanted to do more with solving the underlying causes of disease, and changed tack to pursue genome editing.

“I set out on this journey to understand how we could, and how we could best actually solve those underlying problems of disease,” Oakes explained in an interview. That led to him pursuing research in Zinc-Finger Nuclease (ZFN)-based genome editing – a precursor technique to CRISPR that was far less specific and much more work-intensive and time consuming. Doudna’s groundbreaking paper on CRISPR was published in 2012, and Oakes immediately saw the potential, so he joined her lab at Berkeley.

Meanwhile, Staahl was looking at treatment for disorders that specifically lead to neural degeneration – something that had not previously been part of Doudna’s lab’s research prior to him joining.

“He spent several years in the lab, developing strategies for neurons, and really trying to bring that technology to a point where it could be deployed as a real treatment for neurodegenerative disease, with Huntington’s as a model,” Doudna told me. “So Ben and Brett met up, they came from very different backgrounds, they had really different scientific training originally, but they hit it off. And they saw a really exciting opportunity to use the kind of technology development that Ben had been doing, and that he was very keen on continuing, and to focus it on this challenge of neurodegeneration.”

The result is Scribe Therapeutics, which has already raised $20 million in a Series A funding round (plus some small amount of earlier seed financing contributed by the founders) led by Andreessen Horowitz . Scribe has been at work on their solution since 2018, but remained mostly quiet about their progress until Oakes felt confident that what they’re presenting is a real, viable technology that can be used to produce therapeutics now. Representative of that progress, the company is also announcing a new collaboration with large drugmaker Biogen, Inc. to collaborate on CRISPR-based medecines for treating neurological diseases, and specifically Amyotriophic Lateral Sclerosis.

That deal is valued at $15 million in upfront commitments, with as much as $400 million or more in milestone payouts to follow, as well as royalties attached to any shipping therapeutics that result. Oakes says it’s a testament to the maturity of their platform that they were able to secure this partnership. But Scribe will also be pursuing development of its own therapeutics in-house, while partnering where it makes sense – a strategy Oakes says is in service of addressing the greatest number of possible disease treatments the startup can manage. And while it’s already generating revenue, and Oakes says he’s in no rush to secure additional funding, he does believe that ultimately they will seek out additional investment in order to help ensure they can treat as many potential conditions as possible, as quickly and safely as possible.

As for the fundamental science behind Scribe, their advantage lies in the work they’ve done to adapt a molecule called CRISPR-CasX, which is a bit smaller than Cas9 and not derived from pathogen molecules, both of which make it better-suited to therapeutics. Scribe has spent the past year-and-a-half turning CasX into the basis of a platform that works better than any CRISPR protein that exists for delivery via adeno-associated virus (the current state-of-the-art in gene therapy delivery), as well as engineering it for greater specificity.

“We built Scribe specifically to do that, to build an engineering core focused exclusively on making the most advanced the very best therapeutic genome editing molecules that we could,” Oakes said.

#andreessen-horowitz, #biology, #biotech, #biotechnology, #crispr, #disease, #emerging-technologies, #genetic-engineering, #health, #jennifer-doudna, #life-sciences, #model, #science, #tc, #technology-development

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Mammoth Biosciences lands exclusive license to new CRISPR proteins that could boost gene editing precision

CRISPR pioneer Mammoth Biosciences has secured an exclusive license to a new family of CRISPR proteins, from UC Berkeley, which covers R&D and commercialization across all potential fields. This is a significant addition to Mammoth’s intellectual property holdings, since this new family of CRISPR proteins, known as the Casɸ family, is roughly half the size of Cas9, the protein that effectively launched CRISPR to begin with.

In CRISPR, size actually matters quite a lot – the smaller size of Casɸ could help this new protein family excel in areas including the exact precision of gene editing, as well as easing delivery for use in actual living cells, and combining different target edits in a so-called ‘multiplex’ arrangement.

In July, a peer-reviewed paper published in Science detailed the discovery of Casɸ and outlined its potential advantages for use in CRISPR gene editing. Casɸ was discovered in bacteriophages, which is a type of virus that infects and replicates within bacteria – their literal translation is “bacteria eater.”

Increasing accuracy in CRISPR-based genetic editing has been an ongoing goal in the industry, with various approaches conceived and developed to help mitigate what is known as “off-target” activity, or unintended edits and genetic modifications that can occur when using the original Cas9-based editing approaches.

Mammoth Biosciences was founded by CRISPR co-discoverer Jennifer Doudna, and Douda’s lab at UC Berkeley is the source of the new discovery. This definitely helps strengthen its portfolio, and could lead to significant potential upside to the business through eventual commercialization.

#biology, #biotech, #biotechnology, #crispr, #genetic-engineering, #health, #life-sciences, #mammoth-biosciences, #science, #tc, #uc-berkeley

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Mammoth Biosciences’s CRISPR-based COVID-19 test receives NIH fundings through RADx program

CRISPR tech startup Mammoth Biosciences is among the companies that revealed backing from the National Institutes of Health (NIH) Rapid Accleration of Diagnostics (RADx) program on Friday. Mammoth received a contract to scale up its CRISPR-based SARS-CoV-2 diagnostic test in order to help address the testing shortages across the U.S.

Mammoth’s CRISPR-based approach could potentially offer a significant solution to current testing bottlenecks, because it’s a very different kind of test when compared to existing methods based on PCR technology. The startup has also enlisted the help of pharma giant GSK to develop and produce a new COVID-19 testing solution, which will be a handheld, disposable test that can offer results in as little as 20 minutes, on site.

While that test is still ind development, the RADx funding received through this funding will be used to scale manufacturing of the company’s DETECTR platform for distribution and use in commercial laboratory settings. This will still offer a “multi-fold increase in testing capacity,” the company says, even though it’s a lab-based solution instead of a point-of-care test like the one it’s seeking to create with GSK.

Already, UCSF has received an Emergency Use Authorization (EUA) from the FDA to use the DETECTR reagent set to test for the presence of SARS-CoV-2, and the startup hopes to be able to extend similar testing capacity to other labs across the U.S.

#articles, #biology, #biotech, #biotechnology, #coronavirus, #covid-19, #crispr, #fda, #genetic-engineering, #health, #mammoth-biosciences, #national-institute-of-health, #science, #startup-company, #tc, #tech-startup, #united-states

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A ‘Cure for Heart Disease’? A Single Shot Succeeds in Monkeys

A novel gene-editing experiment seems to have permanently reduced LDL and triglyceride levels in monkeys.

#cholesterol, #genetic-engineering, #genetics-and-heredity, #heart, #international-society-for-stem-cell-research, #kathiresan-sekar, #monkeys-and-apes, #rna-ribonucleic-acid, #triglycerides

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I Tried to Grow a Pandemic Garden. My Strawberry Seedling Got a Virus.

Plants can get sick, too.

#agriculture-and-farming, #corn, #flowers-and-plants, #genetic-engineering, #strawberries

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Even My Strawberry Seedling Has a Virus

Plants can get sick, too.

#agriculture-and-farming, #corn, #flowers-and-plants, #genetic-engineering, #strawberries

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Emerging from stealth, Octant is bringing the tools of synthetic biology to large scale drug discovery

Octant, a company backed by Andreessen Horowitz just now unveiling itself publicly to the world, is using the tools of synthetic biology to buck the latest trends in drug discovery.

As the pharmaceuticals industry turns its attention to precision medicine — the search for ever more tailored treatments for specific diseases using genetic engineering — Octant is using the same technologies to engage in drug discovery and diagnostics on a mass scale.

The company’s technology genetically engineers DNA to act as an identifier for the most common drug receptors inside the human genome. Basically, it’s creating QR codes that can flag and identify how different protein receptors in cells respond to chemicals. These are the biological sensors which help control everything from immune responses to the senses of sight and smell, the firing of neurons; even the release of hormones and communications between cells in the body are regulated.

“Our discovery platform was designed to map and measure the interconnected relationships between chemicals, multiple drug receptor pathways and diseases, enabling us to engineer multi-targeted drugs in a more rational way, across a wide spectrum of targets,” said Sri Kosuri, Octant’s co-founder and chief executive officer, in a statement.

Octant’s work is based on a technology first developed at the University of California Los Angeles by Kosuri and a team of researchers, which slashed the cost of making genetic sequences to $2 per gene from $50 to $100 per gene.

“Our method gives any lab that wants the power to build its own DNA sequences,” Kosuri said in a 2018 statement. “This is the first time that, without a million dollars, an average lab can make 10,000 genes from scratch.”

Joining Kosuri in launching Octant is Ramsey Homsany, a longtime friend of Kosuri’s, and a former executive at Google and Dropbox . Homsany happened to have a background in molecular biology from school, and when Kosuri would talk about the implications of the technology he developed, the two men knew they needed to for a company.

“We use these new tools to know which bar code is going with which construct or genetic variant or pathway that we’re working with [and] all of that fits into a single well,” said Kosuri. “What you can do on top of that is small molecule screening… we can do that with thousands of different wells at a time. So we can build these maps between chemicals and targets and pathways that are essential to drug development.”

Before coming to UCLA, Kosuri had a long history with companies developing products based on synthetic biology on both the coasts. Through some initial work that he’d done in the early days of the biofuel boom in 2007, Kosuri was connected with Flagship Ventures, and the imminent Harvard-based synthetic biologist George Church . He also served as a scientific advisor to Gen9, a company acquired by the multi-billion dollar synthetic biology powerhouse, Ginkgo Bioworks.

“Some of the most valuable drugs in history work on complex sets of drug targets, which is why Octant’s focus on polypharmacology is so compelling,” said Jason Kelly, the co-founder and CEO of Gingko Bioworks, and a member of the Octant board, in a statement. “Octant is engineering a lot of luck and cost out of the drug discovery equation with its novel platform and unique big data biology insights, which will drive the company’s internal development programs as well as potential partnerships.”

The new technology arrives at a unique moment in the industry where pharmaceutical companies are moving to target treatments for diseases that are tied to specific mutations, rather than look at treatments for more common disease problems, said Homsany.

“People are dropping common disease problems,” he said. “The biggest players are dropping these cases and it seems like that just didn’t make sense to us. So we thought about how would a company take these new technologies and apply them in a way that could solve some of this.”

One reason for the industry’s turn away from the big diseases that affect large swaths of the population is that new therapies are emerging to treat these conditions which don’t rely on drugs. While they wouldn’t get into specifics, Octant co-founders are pursuing treatments for what Kosuri said were conditions “in the metabolic space” and in the “neuropsychiatric space”.

Helping them pursue those targets, since Octant is very much a drug development company, is $20 million in financing from investors led by Andreessen Horowitz .

“Drug discovery remains a process of trial and error. Using its deep expertise in synthetic biology, the Octant team has engineered human cells that provide real-time, precise and complete readouts of the complex interactions and effects that drug molecules have within living cells,” said Jorge Conde, general partner at Andreessen Horowitz, and member of the Octant board of directors. “By querying biology at this unprecedented scale, Octant has the potential to systematically create exhaustive maps of drug targets and corresponding, novel treatments for our most intractable diseases.”

#andreessen-horowitz, #articles, #biology, #biotechnology, #chemicals, #dna, #dna-sequencing, #dropbox, #drug-development, #drug-discovery, #emerging-technologies, #executive, #flagship-ventures, #general-partner, #genetic-engineering, #genetics, #george-church, #ginkgo-bioworks, #google, #harvard, #jason-kelly, #jorge-conde, #pharmaceutical, #synthetic-biology, #tc

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A Coronavirus Vaccine Project Takes a Page From Gene Therapy

The technique aims to make a person’s cells churn out proteins that will stimulate the body to fight the coronavirus.

#coronavirus-2019-ncov, #fazzalari-emilia, #freeman-mason-w, #genetic-engineering, #grousbeck-wyc, #harvard-university, #massachusetts-eye-and-ear, #massachusetts-general-hospital, #vaccination-and-immunization, #your-feed-healthcare

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Can Genetic Engineering Bring Back the American Chestnut?

The tree helped build industrial America before disease wiped out an estimated three billion or more of them. To revive their lost glory, we may need to embrace tinkering with nature.

#agriculture-and-farming, #american-chestnut-foundation, #genetic-engineering, #genetics-and-heredity, #trees-and-shrubs

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