Daily Archives: October 22, 2019

Running short: Neurons from mice missing SCN2A (right) have signal-receiving branches that are less mature than those in controls (left).

Injecting the gene-editing tool CRISPR into the brains of adolescent mice counteracts the effects of a mutation in a top autism gene. The finding suggests that mutations in this gene, SCN2A, may be treatable at any age.

This gives us hope that this is something thats not just a developmental deficit, and that once all the changes are there that youre stuck with them, says Perry Spratt, a graduate student in Kevin Benders lab at the University of California, San Francisco. Spratt presented the unpublished findings today at the 2019 Society for Neuroscience annual meeting in Chicago, Illinois.

SCN2A encodes a sodium channel that helps neurons propagate electrical signals. The mice have a harmful mutation in one copy of the gene, causing their neurons to fire sluggishly and make immature connections. The treatment reverses the problem by ramping up expression of the intact copy.

The first inkling that the reversal might work even after infancy came in June: The team reported then that introducing an SCN2A mutation into adolescent mice has many of the same effects on neurons as a mutation present from conception.

At the cellular level we see a lot of the same deficits as we see when the genes been gone throughout life, Spratt says.

The team engineered mice in which the mutation in SCN2A can be corrected by injecting an enzyme called Cre recombinase.

Injecting the Cre enzyme into the brains of 4- to 5-week-old mutant mice restored normal expression of SCN2A. It also reversed the problems in the mices neurons.

But this strategy cannot be applied to people because it would require genetic engineering of embryos. So the researchers created a virus that ferries a modified version of CRISPR into cells. This version of the editing tool does not snip DNA but can instead activate any gene.

The researchers injected the virus into the brains of 4-week-old mutant mice, along with synthetic RNA snippets designed to guide CRISPR to SCN2A. The treatment boosted SCN2A expression and reversed the problems in the mices neurons.

The team also tested one important control: They found that the treatment does not cause neurons to become hyperactive and so does not run the risk of triggering seizures.

The remarkable thing about this is that it can go gangbusters without making the cells hyperexcitable, says Bender.

The team is testing ways to deliver the virus to the whole brain. They also plan to test whether CRISPR reverses learning and memory problems in the mutant mice.

For more reports from the 2019 Society for Neuroscience annual meeting, please click here.

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CRISPR therapy may reverse autism mutation's effects well past infancy - Spectrum

The ability to read genomes has transformed our understanding of biology. Being able to write them would give us unprecedented control over the fabric of life.

Rapid advances in DNA sequencing and gene editing technology mean we are now truly in the age of genomics. For a few hundred dollars, genetic testing companies will give you a detailed rundown of your ancestry and susceptibility to a host of diseases. The first genetically modified humans are about to turn one.

The advent of CRISPR in particular has given us the ability to tweak DNA with incredible precision, but were still largely restricted to switching specific genes on and off or swapping one gene for another. The field of synthetic biology wants to change that by bringing engineering principles to biology.

But theres a long way to go, and a group of leading geneticists have now laid out the technology roadmap required to get there, published last week in a policy paper in Science. Here are the four areas where we need to step up our game.

The ultimate goal of genetic modification is to produce a change in the phenotypethe outward characteristicsin the target organism. But most complex traits are the result of a complicated interplay between multiple genes and an organisms environment, so mapping how DNA tweaks will translate into desired attributes is challenging.

Large-scale genome design will require computer programs that can do this accurately and efficiently. While projects like Synthetic Yeast 2.0 have made the first steps in this direction, the field needs to build complex new models that can predict the results of changes to the genome sequence.

These could still be decades away, but using machine learning to mine the wealth of biology data in public databases could accelerate them. Programs that can automate the design of experiments to cut down the number of rounds of design will also be required, as will the adoption of common data standards to enable collaboration.

Weve been able to synthesize DNA for decades, but the most common approach is restricted to short sections of DNA just a few hundred base pairs long. Building entire genomes requires long sequences of several thousand base pairs, so currently scientists rely on a laborious and error-prone process of stitching many smaller DNA sections together.

Large-scale genome engineering will require much faster, cheaper, and more efficient methods for DNA assembly. One nearer-term possibility is designing new enzymes that can reduce the number of errors and therefore boost the yield of the process. But in the long run, new technologies that can produce long and accurate sequences offer far more potential, and there are some promising enzyme-based approaches that may fit the bill.

While our gene-editing prowess has come a long way, we still struggle to make widespread changes to a genome simultaneously. If we could develop this capability, it could significantly decrease the amount of time it takes to modify organisms and even sidestep the need to build genomes from scratch.

This will mean finding ways to prevent the multitude of guide RNAs (the homing devices that tell CRISPR where in the genome to make changes) required for simultaneous edits to multiple genes from interfering with each other.

It will also be necessary to create libraries of tools for making changes across the genome and accessibility maps that highlight how efficiently different targets can be altered. These will make it easier for scientists to plan where to make changes to achieve their desired results and form the basis of predictive computer models that can streamline the process.

DNA is more than just a string of genes; its packaged into chromosomes, whose number and shape vary across species. Our ability to assemble and manipulate these chromosomes is still rudimentary.

Most efforts so far have relied on yeast to do this for us, and it has been able to deal with viral, bacterial, yeast, and algal chromosomes, as well as fragments of mice and human genomes. But engineering more specialized artificial chromosomes looks to be beyond yeast, so we need to find newer, more flexible organisms that can do this.

Transplanting these chromosomes into the target organism is also a major bottleneck. Techniques like cell fusion and microinjection show promise, but require funding for multidisciplinary work to bridge the gap between microfluidics research and molecular biology. Theres also a need for greater understanding of the fundamental forces that govern the architecture of chromosomes and how they interact.

Achieving all this could take decades, and will require the same kind of massive cross-disciplinary effort seen in the Human Genome Project. It will also require concerted government funding and close involvement of the private sector if its going to become a reality. But the benefits of harnessing the ability to write genetic code from scratch could be enormous for the biomedical, pharmaceutical, agricultural, and chemical industriesand for humanity as a whole.

Image Credit: Zita/Shutterstock.com

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With These 4 Breakthroughs, We'll Be Able to Write Whole Genomes From Scratch - Singularity Hub

With everything youve been hearing about genetic engineering over the years, starting with the idea of genetically-modified fruits and vegetables all the way through gene editing in humans, youve heard a lot about why itshouldnt be done. But what are the positives? And what might happen if gene editing goes mainstream and available to (gulp) everyone? A new Netflix docuseries examines that issue.

Opening Shot: At night, we see a large cage full of barking dogs, likely pit bulls. The location is Mendenhall, Mississippi.

The Gist: The dogs are owned by Paul Ishee, an oil field tech who breeds dogs on the side. He collects sperm from the dogs (in just the way youd expect) because he wants to genetically engineer a better dog. How does he do that? Via CRISPR, a small protein that can be injected via a bacteria into an organism to edit its DNA. One of the big features with CRISPR, which was perfected only a few years ago, is that the protein is easily obtainable. So genetic modifications can be done in expensive labs by trained scientists or by biohackers in their garages.

Unnatural Selection, a docuseries produced and directed by Leeor Kaufman and Joe Egender, examines the new frontier of genetic engineering, and what ethical stumbling blocks there are to adapting gene editing on a wider basis.

The filmmakers interview a mixture of scientists and biohackers, some of whom are both. Dr. Jennifer Doudna, widely regarded as the inventor of the CRISPR method, seems to be in the middle of the debate; she knows how powerful using CRISPR can be when it comes to curing genetic-based diseases and other conditions, but is wary of people who want to use it to engineer superior organisms. Biohackers like Dr. Josiah Zayner, a biophysicist who used to work for NASA, is in favor of the democratization of genetic engineering, sending $140 CRISPR kits to people via Priority Mail. One of those people is Ishee, who wants to make a glowing dog as his first experiment, just to prove that the engineering worked.

Others, such as Dr. Kevin Esvelt, an evolutionary engineer at MIT, want to put genetic engineering into practice by modifying mice to be immune to the bite of Lyme-carrying ticks and then releasing them to breed on a small island in Marthas Vineyard. What will the consequences of that be? Even Esvelt really doesnt know for sure. And thats the problem, and where the ethical issues take hold. Sending genetically modified mice, dogs, or humans into the world may introduce unintended consequences, or might be deadly in the wrong hands. But are people who think its dangerous just being alarmist?

Our Take: Genetic engineering and all of its advantages and ethical quandaries is a complex topic to cover, and in the first part of their four-part docuseries, Kaufman and Egender try to lay out the issue in as balanced a way as possible. But what we got during the feature-length (70-minute) first episode was more of a sense of fear than one of wonder.

Why? Because, while the filmmakers are giving biohackers like Ishee and Dr. Zayner as much time as the more legit scientists, it doesnt help matters when you see Dr. Zayner concocting CRISPR samples in his kitchen or see Ishee looking at YouTube videos of glowing mice and luminescent monkeys for inspiration.

But then we see Jackson Kennedy, a boy from New Jersey who is autistic and was born with poor vision, and we become hopeful again. His parents got genetic testing for him that showed that hes missing a gene that would help him see. And hes going to go for treatment that fixes that gene, which should restore his sight if it works. This is where genetic engineering could make a huge positive impact on the world. But, whether the filmmakers intended it this way or not, there seems to be a whole lot scarier ways the use of CRISPR could go haywire, which makes us as cautious as the anti-engineering activists they interview for the first episode.

Parting Shot: We see Jason right before he goes in for the procedure, excited at the prospect that he might see more than just shapes for the first time.

Sleeper Star: When Jasons mother talked about how he wanted to be an astronaut and how heartbroken he was when he heard that astronauts need 20-20 vision, it almost broke our hearts. While his story will be a through-line through the limited series, were disappointed that there isnt a documentary just about him.

Most Pilot-y Line: There are actually two scenes of Ishee collecting sperm from his dogs. Yuck.

Our Call: STREAM IT. Were wondering how much of what were going to see during the rest ofUnnatural Selection will be more crackpots and less of the positive stuff like Jasons treatment. If its the former, wed likely end up skipping it.

Joel Keller(@joelkeller) writes about food, entertainment, parenting and tech, but he doesnt kid himself: hes a TV junkie. His writing has appeared in the New York Times, Slate, Salon,VanityFair.com,Playboy.com, FastCompany.com,RollingStone.com, Billboard and elsewhere.

StreamUnnatural Selection On Netflix

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Stream It Or Skip It: 'Unnatural Selection' On Netflix, A Docuseries About The Ethics And Ease Of Editing DNA - Decider

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The rise and emergence of technology has truly seen the birth of a completely new and exciting digital age, which has transformed the globe as a result. Innovation and advancements has seen technology grow not only across industries and a variety of businesses but also our personal lives, as we all interact with new devices without even realizing how much we use them on a daily basis.

With technology becoming intertwined and cemented into the 21st century way of living, we have seen the birth of the Fourth Industrial Revolution, which is significantly different from the first revolution back in the 18th century. This new and leading way of production is rapidly changing the manufacturing process across the globe, with the rise of complicated and impressive technologies, such as robotics, 3D printing, genetic engineering, the Internet of Things (IoT), and artificial intelligence. These innovations are being increasingly implemented into all industries, businesses and processes to improve production and boost efficiency.

As a result of the Fourth Industrial Revolution, production levels have improved drastically, with technologies greatly enhancing the speed and accuracy of processes that were often considered tedious and slow, with more room for human error. But in this new production revolution, who is leading the way in embracing these new innovations?

RS Components have produced a graphic analyzing data from the World Economic Forums Readiness for the Future of Production report, to reveal the countries adopting these technologies and leading the way in the future of production as a result. With each country analysed by a series of metrics including global trade and investment, institutional framework, sustainable resources, demand environment and emerging technologies, the countries leading production levels forward have been scored out of 10 to reveal who has come out on top.

The top 10 countries driving the future of production include:

US 8.16

Singapore 7.96

Switzerland 7.92

UK 7.84

Netherlands 7.75

Germany 7.56

Canada 7.56

Hong Kong 7.45

Sweden 7.40

Denmark 7.20

At the top of the leaderboard is the US with an impressive score of 8.16 out of 10. The US dominates the top of each metric excluding Sustainable Resources and Institutional Framework.

With the country holding enormous opportunity and access to digital technologies, it is important for manufacturers to capitalize on this and ensure their employees are prepared for the exciting future of production ahead. The US is known for its innovation and it is its advances, stable and connected technological platform it has built up over the years that allows it to lead the world in the future of production, from research to the manufacturing stage.

Singapore ranks as the second country driving the future of production with a score of 7.96 and Switzerland in third at 7.92. With around 20 percent of its GDP deriving from manufacturing, it is unsurprising that Singapore sits as the worlds fifth largest refinery export hub and among the top 10 global chemical hubs by export volume. Singapore, manufacturers are capitalizing on robots, artificial intelligence and predictive analytics.

Preparing employees for the future of production

With many countries making significant efforts to increase their technological innovations in their production processes, it is important for businesses and industries to address the need to prepare its employees for the change. Educating employees on new technologies and also incorporating information on these advancements into school curriculum will be greatly beneficial in preparing a technologically innovative nation.

With this preparation combined with the technological opportunity for industries and nations to explore, the world of production and manufacturing is set to change astronomically.

What country will be leading the way in the future of production in 10 years time?

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INFOGRAPHIC: The Countries Leading the Way in the Future of Production - BOSS Magazine

Its too early to write off farm animals just yet, says Darren Streiler, investment director at ADM Ventures (ADMs corporate venturing arm, which has invested in Geltor, Perfect Day and Sustainable Bioproducts), but this technology is rapidly moving from the laboratory to the real world.

At this stage, a lot of these companies are reaching Series B and they are raising significant amounts of funding and a lot of these companies have pilots that have now been performing for a number of years, said Streiler, who was speaking to FoodNavigator-USA at Rabobanks FoodBytes! pitch competition in Chicago last month (where he served as one of the judges).

So wed characterize this space particularly in the mycoprotein and the fermentation-based and the cell cultured space, all in all, there are probably around 100 companies at this time.

What interesting is that were really able to scale these technologies. For instance, ADM has some of the largest fermentation tanks in the US, and with one of our startups Perfect Day, we have ajoint development agreementto manufacture their fermentation-based dairy proteins. We have 250,000 liter tanks that could really scale this type of technology.

Asked whether proteins produced in cultivators/fermentation tanks/bioreactors (proponents are still arguing over the most consumer-friendly terminology) could ultimately account for a bigger market share than plant-based proteins, he said:Not every type of protein is going to fit every type of customer.

"We see segments in the market and were aiming to provide options to satisfy all of those different segments.

Producing protein from microbes has certain obvious advantages, say startups in the space.

For a start, instead of growing a living breathing animal just to break it down into products, they are designing the most efficient process to produce just the components we need, which can be manufactured from a distributed network of local production facilities (fermentation tanks) using a fraction of the land, water, and inputs required to raise and feed animals.

(Not to mention, it also doesnt involve raising and slaughtering animals on an industrial level.)

The resulting ingredients have the added appeal of consistent quality, a lack of price volatility, and security of supply.

While several food ingredients from enzymes to sweeteners, vitamins, colors, and the heme protein in the Impossible Burger are already produced by tiny microorganisms, a new wave of startups is using microbes to produce things currently produced by mammals, from whey and casein proteins and egg white to sugars and proteins found in human breast milk.

Some companies such asMotif FoodWorks use synthetic biology to write DNA sequences that can be inserted into microorganisms to instruct them to produce animal proteins; others such asSustainable Bioproductshave identified microbes that naturally produce new to the world proteins; while others such asNoblegen are working with microorganisms that can be coaxed into producing multiple high-value ingredients without using genetic engineering.

Others such asAir Protein(which utilizes single-cell organisms called hydrogenotrophs first studied by NASA in the 1960s),Solar Foods,NovoNutrientsandDeep Branch Biotechnologyare converting components found in the air - notably carbon dioxide (which can be recycled from industrial waste) - into proteins.

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WATCH: What role will microscopic microbial factories play in the future of protein? - FoodNavigator-USA.com