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GMOs, 3D-Printed Chocolate, And The Rapid Development Of Food Technology

– Contributed Content –

Golden rice

(International Rice Research Institute, Wikimedia Commons)

3 August 2016. The human population is growing faster than ever, and as we shoot towards a headcount of nearly 9 billion, the need for cutting-edge food technology is increasing with it. Land is becoming more sparse, and distant communities more connected, and food security is a bigger issue than ever before. It’s not all doom and gloom though! New, emerging technology is assisting us to analyze, track and organize the way we produce and consume food. It’s all working towards reduced waste, carbon emissions, and a world that won’t go hungry. Being able to order takeaways with your phone is only the tip of the iceberg. Here are some of the food technologies which are changing the world we live in.

We’ll start this list off with possibly the most controversial food technology; GMOs. The technology used to create genetically modified organisms, or GMOs, is as essential to our food industries as it is notorious. As a basic definition, a GMO is anything organic which has undergone genetic engineering to grow with certain traits. Probably the most common form of GMO is crops which have been made to have a natural resistance to pests or herbicides. On the lighter side of so-called “Franken-food”, some crops have been genetically fiddled to have more nutritious value. Since the first genetically modified tomato was put on the market in 1994, the niche has swelled to become an incredibly lucrative industry. Of course, genetically modified foods have brought on a pretty heavy backlash, while breathing life into organic and vegan companies. Check out this Hampton Creek product info for one example. GMO labels are mandatory in Europe, whereas the States still hasn’t passed any formal regulations. Today, there are certain crops in development which will be able to grow outside of its native habitat, like wheat and rice. While we’re toying with nature even more here, it’s expected to increase crop yield and put a dent in food shortages.

Next, precision agriculture. You may have heard of this technology referred to as “satellite farming”. This refers to the use of GPS and satellite imaging to track soil levels, crop yields, and even weather patterns in order to increase farming efficiency. This may just sound like another way to remove human interaction from production, but it’s expected to have a profound, positive effect on the amount of food in the world. This makes the technology behind precision farming all the more important when we’re looking at a population of 9 billion by 2050. When a farmer’s kitted out with a precision agricultural system, they’re able to use a simple interface to pinpoint one specific area of land, and see how productive it is. When the fist precision agricultural systems were released in the nineties, an entire field was treated as a single unit. With all this information at farmers’ fingertips, they’re able to avoid wasting seed, pesticides and fertilizers. The development of this technology has also drawn the attention of the international green lobby. Through precision agriculture, farmers are able to run their farm in a more sustainable way, and avoid wasting important resources like water.

Food in garbage can

(U.S. Department of Agriculture, Flickr)

Food waste tracking is another emerging technology which is going to have some big effects on the global food industry. Feeding America estimates that between 25 and 40 per cent of all the food sold in the US is thrown away every year. The campaign against food waste has been going on for decades, for obvious reasons. It’s only now, just after the social media revolution, that we’re seeing technology contribute to it. Dozens of apps and web platforms have been springing up in recent years, all focused on making sure that food reaches people’s mouths, rather than the bin. Leloca, for example, is an app made to help restaurants minimize the food waste that happens in their day-to-day business. It gives consumers deals on food which get up to 50% off, within 45 minutes of a posting from the restaurant. Another popular app, called 222 Million Tons, allows you to enter your household size and food preferences, then calculates a shopping list made to minimise waste. There’s even a kind of leftovers Tinder, called Leftoverswap. This lets people with leftover food match with others in the area, who’d like to purchase cheap produce and pick it up. That last one sounds like it may have some Uber-like controversy on the horizon. Still, the gradual reduction of food waste is sure to have a big impact on the food industry as a whole.

Next, 3D printing. I know, when you hear the term you probably don’t think about food straight away. However, recent applications of the new technology have given birth to 3D Systems’ own model designed specifically for food. The firm, currently one of the biggest corporate giants in the 3D printing industry, even had a brief stint with Hershey’s chocolate, and made customized chocolate shapes. NASA has also been known to make a 3D-printed pizza, which is apparently a step forward for astronauts’ food. The start-up Modern Meadow is also using 3D printers in the production of meat-free meat. Most of us associate 3D printers with the manufacturing sector, but the food industry may have pushed us further towards seeing one in every home. The Foodini is a 3D printer designed to fit conveniently on a kitchen counter. You simply prepare your ingredients with a blender, feed it into the unit, and the printer makes whatever shape you want out of the mixture. This may not be the most urgent use for food technology. However, you can’t deny how exciting the coming developments in 3D printed food are going to be!

Going back through all these developing technologies, I’m really starting to feel like I’m living in a sci-fi. These technologies and more are already making a huge impact on every business in the food sector, and they’re still only in their most primitive stages! As time goes on, there’s no telling what kind of tech we’ll see influencing the way we eat.

This post is contributed to Science & Enterprise.

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Electronic Tattoo Measures Blood Alcohol Level

Blood-alcohol measurement patch

Blood-alcohol measurement patch (University of California, San Diego)

3 August 2016. A flexible electronic device worn on the skin like a tattoo can assess blood alcohol level and transmit the results to a nearby mobile phone. Engineers from the labs of Joseph Wang and Patrick Mercier at University of California in San Diego describe their device in a recent issue of the journal ACS Sensors (paid subscription required). Wang and Mercier are director and co-director respectively of the university’s Center for Wearable Sensors.

The UC-San Diego team is seeking more reliable and fool-proof methods for monitoring the level of alcohol in the blood, an issue with implications for public health and safety. Today’s standard testing technology is the breathalyzer, which can return false results if administered immediately after taking a drink or using mouthwash to mask the exhaled alcohol.  A pinprick drop of blood provides more accurate measurements, but is medically invasive and difficult to administer for police officers at a traffic stop.

Researchers from Wang’s nanobioelectronics lab and Mercier’s  microsystems group took a different approach to the problem, focusing on indicators of alcohol content in perspiration, which can provide real-time measurement. Up to now, devices for measuring blood alcohol levels in perspiration were not portable or easy to wear. In addition, the device needs to work even if the person wearing it is not perspiring from exercise or other reasons.

To meet these requirements, the UC-San Diego team devised a wearable patch with both the ability to induce perspiration where worn on the skin and the electronics to measure the blood alcohol levels, as well as transmit the data to a receiver nearby.  The patch has a thin layer of hydrogel, a water-based polymer material, containing pilocarpine, a drug given to treat dry mouth, a condition caused by an autoimmune disorder or a result of X-ray treatments for head and neck cancer. In this case, the moisture-generating properties of the drug are directed into the skin by a mild electric current to induce sweat.

The patch contains electrodes coated with an enzyme, which in the presence of ethanol — the chemical name for alcohol in drinks — reacts to form hydrogen peroxide. Electrodes with a compound called Prussian Blue detect the hydrogen peroxide, and send electric signals through circuitry in the patch, then transmitted to an external device via Bluetooth links. A smartphone app, written in Mercier’s lab, analyzes and displays the results.

The researchers evaluated a prototype of the patch in a proof-of-concept test with 9 healthy volunteers, taking measurements of blood alcohol content before and after consuming 1 beer or a glass of wine. The before-and-after measurements show the device can record differences in blood alcohol content, even when the the device was bent or shaken, which suggests it could be used in practical day-to-day situations.

“Lots of accidents on the road are caused by drunk driving,” says Wang in a university statement. “This technology provides an accurate, convenient, and quick way to monitor alcohol consumption to help prevent people from driving while intoxicated.”He adds that the device could be integrated into a car’s ignition interlock, or even just alert friends that a person is too drunk to drive.

The team plans to increase its alcohol-monitoring capability to 24 hours, as well as expand the platform to measure other types of biochemical reactions.

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Amgen, Advaxis Partner on Personal Cancer Immunotherapy

Listeria monocytogenes bacteria

Listeria monocytogenes bacteria (Nathan Reading, Wikimedia Commons)

2 August 2016. Biological drug maker Amgen is licensing precision immunotherapy technology from Advaxis Inc. to develop treatments for cancer. The deal could bring Advaxis, a biotechnology company in Princeton, New Jersey, as much as $540 million if all parts of the agreement are exercised.

Advaxis develops immunotherapies for cancer from weakened Listeria monocytogenes or Lm bacteria, associated by most people with food poisoning. The bacteria are engineered to include a form of listeriolysin O, a protein that enhances their ability to penetrate cell membranes, in this case tumor cells.

Once inside the tumor cells, the listeriolysin O proteins make cancer cells, which normally hide from the immune system, look like bacteria and generate a response from T-cells in the immune system. In addition, the engineered proteins break down myeloid-derived suppressor and regulatory T-cells that protect the immediate tumor environment.

The agreement gives Amgen an exclusive worldwide license to develop and commercialize an advanced extension of the Advaxis Lm technology, known as My Immunotherapy Neo-Epitopes, or Mine. With Mine, DNA is extracted and sequenced from the patient’s primary tumor or metastatic cancer cells to identify epitopes, binding locations on neoantigens, which are recently formed and not yet recognized by the immune system. These neoepitopes in cancer cells, derived from DNA sequenced from the patient, then become the targets for activated immune system T-cells.

Under the agreement, Advaxis will lead initial research and development of Mine through proof-of-concept, and retain responsibility for manufacturing. Amgen will be responsible for clinical development and commercialization. Clinical trials are expected to begin in 2017.

The deal also calls for Amgen to make an initial payment of $40 million and take an equity stake in Advaxis of $25 million in common stock. Advaxis will also be eligible for development, regulatory, and sales milestone payments of up to $475 million, as well as royalties on product sales.

Amgen is a biotechnology enterprise developing original biological-based treatments as well as biosimilars. The Thousand Oaks, California company has a number of new therapies for cancer in its pipeline currently in clinical trials.

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Commercial Data Yield Genetic Links to Depression

Worried woman

(Ryan McGuire, Pixabay)

2 August 2016. An analysis of data from commercial genetic tests identified 15 regions in the genome and 17 specific variations associated with depression among people of European descent. The team from Massachusetts General Hospital in Boston and the personal genetics testing company 23andMe reported its findings in yesterday’s issue of the journal Nature Genetics (paid subscription required).

The team, funded by National Institute of Mental Health and led by Mass. General psychiatric geneticist Roy Perlis, sought to pinpoint genetic factors behind depression, a disorder affecting 7.6 percent of the U.S. population age 12 and over in any 2-week period. Centers for Disease Control and Prevention says major depressive disorder, also known as clinical depression, resulted in 8 million visits to U.S. doctor’s offices or hospitals, in 2009-2010.

To identify these genetic factors, Perlis and colleagues needed data from hundreds of thousands of individuals to generate statistically reliable findings, a near-insurmountable task with traditional recruitment methods. Samples this large are needed due to the complex nature of depression and many subtle forms the disorder can take.

Instead, the team gained the cooperation of 23andMe in Mountain View, California, which offers personal genetic testing services for as low as $99.00. The company also asks its customers to volunteer their data for research of this kind, and complete questionnaires where participants give their medical histories, including psychiatric illnesses.

From the database of volunteer genomes, where identifying information is removed, the researchers analyzed common genetic variations in 75,607 individuals of European origin, who reported a diagnosis or treatment for depression. For comparison, the team analyzed data from 231,747 persons also of European heritage, with no reports of depression.

In addition, the researchers integrated the data from 23andMe with an earlier genome-wide association study by the Psychiatric Genomics Consortium, adding data from more than 20,000 individuals of European ancestry, both people with depression and healthy individuals for comparison, whose conditions were verified by clinicians. The team then more closely analyzed regions in the genome with possible depression associations among 45,773 people in the 23andMe database reporting the disorder, and 106,354 individuals without the controls.

The results from all 3 data sets identified 15 regions in the genome showing a reliable statistical association with a diagnosis of depression. The analysis also revealed 17 independent genetic variations called single nucleotide polymorphisms or SNPs revealing a reliable association with depression. SNPs are differences in nucleotides, the DNA base building blocks identified by the letters A, C, G, and T. Most SNPs occur normally in the genetic code, but some of these variations are associated with inherited disorders.

The authors believe the accumulated data collected by commercial genetic testing services like 23andMe offer a valuable resource to find new treatment strategies for depression. “The neurotransmitter-based models we are currently using to treat depression are more than 40 years old, and we really need new treatment targets,” says Perlis in a Mass. General statement.  He notes that a “key takeaway from our study is that the traditional way of doing genetic studies is not the only way that works. Using existing large data sets or biobanks may be far more efficient and may be helpful for other psychiatric disorders, such as anxiety disorders, where traditional approaches also have not been successful.”

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Trial to Assess Anti-Gravity Treadmill for Stress Test

Patient in antigravity treadmill

Patient being fitted in anti-gravity treadmill (University of Cincinnati Medical Center)

1 August 2016. Researchers at University of Cincinnati Medical Center plan to evaluate an anti-gravity treadmill for cardiac stress tests that check for heart disease. The treadmill is made by AlterG Inc. in Fremont, California, and will be tested among individuals with physical conditions that prevent them from using a conventional treadmill.

A cardiac stress test helps reveal symptoms of heart disease, which may not appear in day-to-day life or even in an electrocardiogram, or EKG, in a resting state. After an resting-state EKG, the individual steps on a treadmill, also with EKG leads attached, and walks first slowly and easily, then with increasing speed or incline to increase the heart rate. In cases where the patient cannot exercise, an the drug regadenoson is given to increase heart rate and provide an agent for imaging with a gamma camera for real-time functional scanning.

The anti-gravity treadmill has an air-tight pressurized compartment that supports the individual from the waist down. The compartment is inflated, which suspends a person over the walking surface of the treadmill. By pressurizing the compartment, the weight of the individual on the treadmill is decreased by 25 to 50 percent.

“For those of us who tried it out, the anti-gravity treadmill feels like walking on the moon I suppose,” says internist and radiologist Myron Gerson, in a medical center statement. “The sensation of gravity is much less and we can un-weight the patient by 25 percent, 50 percent or even more.” Gerson is one of the study’s principal investigators.

The clinical trial plans to test the anti-gravity treadmill among some 50 patients with conditions such as knee, foot, or back problems that prevent them from taking a conventional stress test. Participants will be randomly assigned to receive regadenoson or use the anti-gravity treadmill.

Exercise is expected to provide better data than the drug regadenoson. “We are testing two hypotheses,” adds Gerson. “First, is the anti-gravity treadmill safe for these people, and second, can use of the anti-gravity treadmill improve image quality?” Gerson believes improved image quality might be achieved when patients reach target heart rates during their stress tests. Participants in the trial who do not reach target heart rates will instead be given regadenoson.

AlterG first developed the anti-gravity treadmill under contract with NASA to offer astronauts on the International Space Station a way to exercise in a zero-gravity environment. The company now markets a version of the treadmill for rehabilitation clinics. AlterG is donating the treadmill for the trial, which is sponsored by University of Cincinnati.

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GSK, Alphabet Form Bioelectronic Device Venture

Moncef Slaoui

Moncef Slaoui, chair of Galvani Bioelectronics (GlaxoSmithKline)

1 August 2016. Drug maker GlaxoSmithKline, or GSK, and Verily Life Sciences, a division of Alphabet, the parent company of Google, are forming a joint venture to develop miniaturized therapeutic electronic devices. The two partners will provide Galvani Bioelectronics, as the venture is known, with up to £540 million ($715 million) over the next 7 years.

Galvani Bioelectronics plans to discover and develop implanted electronic devices that send signals along nerve pathways in the body addressing chronic diseases. In some cases, these conditions are characterized by distorted signals that the devices are intended to correct. The venture plans to start out investigating bioelectronics as therapies for inflammatory, metabolic, and endocrine disorders. The partner companies say tests with animals already show the technology’s potential with treating type 2 diabetes.

GSK will hold a majority (55%) ownership in Galvani Bioelectronics, with Verily taking the remainder. Contributions from the two companies could reach as high as £540 million if all planned milestones are achieved.

Galvani Bioelectronics is expected to combine GSK’s drug discovery and development experience with Verily’s and Alphabet’s expertise in low-power electronics, miniaturization, software, and data analytics. Both companies are contributing intellectual property needed by the venture.

Moncef Slaoui, who chairs GSK’s vaccines division, will serve as chair of the Galvani Bioelectronics board. Kris Famm, GSK’s vice-president for bioelectronics research will be the company’s president. The new enterprise will be headquartered at GSK’s research center in Stevenage, U.K., with a lab at Verily’s facility in South San Francisco, California. The venture is expected employ 30 scientists, engineers, and clinicians. Galvani also plans to fund collaborations with academic research groups and other companies.

“Many of the processes of the human body,” says Slaoui in a GSK statement, “are controlled by electrical signals firing between the nervous system and the body’s organs, which may become distorted in many chronic diseases. Bioelectronic medicine’s vision is to employ the latest advances in biology and technology to interpret this electrical conversation and to correct the irregular patterns found in disease states, using miniaturized devices attached to individual nerves.”

GSK began its R&D work in bioelectronics in 2012, which the company says resulted in research collaboration with 50 labs worldwide, including successful proof-of-concept tests in lab animals. As reported in Science & Enterprise, GSK started a venture capital fund in 2013 to invest in companies working in developing therapeutics addressing the body’s electrical signaling network.

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Portable On-Demand Biologic Production System Designed

Bioreactor in ambulance

Bioreactor system, left foreground, in a simulated ambulance (Mass. Institute of Technology)

29 July 2016. A portable device that produces small batches of biological drugs, down to a single dose, was shown to generate two different biopharmaceuticals under lab conditions. A description of the system and results of the proof-of-concept test appear in today’s issue of the journal Nature Communications.

The team from the Synthetic Biology group led by bioengineering professor Timothy Lu and affiliated labs at Massachusetts Institute of Technology is seeking techniques for producing drugs from biological processes, such as vaccines and protein treatments. With current technology, biopharmaceuticals require long lead times and must be produced in large batches, making it difficult to serve people in remote locations, emergency conditions, or soldiers on the battlefield. In fact, Defense Advanced Research Projects Agency or DARPA, an agency with a direct interest in this capability, provided funding for the project.

Lu and colleagues designed their device to be an integrated, stand-alone system that could be easily transported and deployed, and produce a range of different biological drugs. Their system is a millimeter-scale bioreactor, measuring 31 x 34 x 36 centimeters, that can be programmed to produce therapeutic proteins on demand to meet certain criteria. The bioreactor contains Pichia pastoris, a strain of yeast that grows quickly and easily. This yeast species grows with ordinary methanol, an inexpensive alcohol, as its energy source, and in high cellular densities.

A key component of the bioreactor is a microfluidic or lab-on-a-chip device with channels, membranes, and chambers for mixing and storing cells and fluids, then pumping out the product. The microfluidic device is a product of the optics and electronic lab led by MIT engineering professor Rajeev Ram, a co-senior author of the paper. The device is also being commercialized by a Pharyx Inc. in Woburn, Massachusetts, a start-up company founded by Kevin Lee, another co-author.

MIT team genetically engineered the yeast for a raw material that could produce different kinds of biologic drugs, which for the proof-of-concept paper were recombinant human growth hormone, a treatment for growth disorders in children, and interferon alpha-2b, an anti-viral protein also approved as a cancer treatment. Each of the engineered yeast varieties was then exposed to a triggering compound:

Beta-estradiol, a form of estrogen, to produce recombinant human growth hormone, and

Methanol, to produce interferon alpha-2b

In each case, the bioreactor succeeded in producing near single-dose quantities of the desired biologic drugs in less than 24 hours. As important, the bioreactor was designed to flush out the product, leaving the engineered yeast cells for producing the proteins, which allows the same system for generating multiple drugs. In a real-life setting, output from the bioreactor would still need analysis and purification before the product could be used as a treatment.

Lu and colleagues are investigating enhancements to the system for generating combinations of antibodies used together, which could affect the often high price of these biologic drugs, since they usually require separate production lines. “But if you could engineer a single strain, or maybe even a consortia of strains that grow together, to manufacture combinations of biologics or antibodies,” says Lu in a university statement, “that could be a very powerful way of producing these drugs at a reasonable cost.”

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Open-Source Discovery Yields Anti-Malaria Candidates

Malaria Box

Malaria Box kit (Medicines for Malaria Venture/University of Washington)

29 July 2016. A worldwide collective research project tested 400 compounds as potential anti-malarial drugs, which led to the start of more than 30 new drug development programs for malaria and other diseases. The open-source initiative is described in yesterday’s issue of the journal PLoS Pathogens.

The project called Malaria Box, organized by the advocacy group Medicines for Malaria Venture, distributed the 400 test compounds to 200 labs in 30 countries between 2011 and 2015. Malaria Box, an actual physical package, contained test kits for the labs to screen the candidates for activity against Plasmodium falciparum malaria parasites transmitted by mosquitoes. In humans, the parasite multiplies in the liver, then infects red blood cells. World Health Organization says the disease occurs in nearly 100 countries, with some 214 million cases reported in 2015, causing up to 438,000 deaths.

The global effort, coordinated by University of Washington medical professor and first author Wesley Van Voorhis, detailed to the project during a sabbatical, sought to accelerate the discovery of new anti-malarial drug candidates, by breaking down institutional barriers between academic and industry labs. The 400 test compounds resulted from an initial screening of more than 25,000 candidates found primarily in industry libraries.

The test compounds in Malaria Box kits were sent free of charge to labs for more detailed analysis on activity against malarial parasites, with the stipulation that their findings be placed in the public domain. Their results were then collected in a standardized format which allowed for efficient meta-analysis.

The findings report on 236 screens of the compounds, which identified 135 candidates that act on the malaria parasite in different ways, and at various stages in parasite’s life-cycle. In addition, participating labs reported hits on a number of other tropical disease pathogens, including parasitic worms and dengue, as well as human cancer cells. The authors say more than 30 new drug development programs, including a colon cancer treatment by National Cancer Institute, can be traced to findings from this initiative.

Medicines for Malaria Venture hopes to duplicate this outcome with a similar program begun in January 2016 called Pathogen Box covering a broader range of infectious agents. Like Malaria Box, this new kit contains 400 test compounds representing tuberculosis, dengue, parasitic worms, Chagas disease, and other tropical diseases, as well as malaria.

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Univ. Spin-Off Develops New Cybersecurity Paradigm

Hacker

(bykst, Pixabay)

28 July 2016. A start-up enterprise from a technology university in Switzerland is developing a simplified cybersecurity infrastructure for businesses, and raised $2 million in its first venture funding round. Cyberhaven, a spin-off company from Ecole polytechnique fédérale de Lausanne, or EPFL, is also opening a new office in Cambridge, Massachusetts.

The company is commercializing a cybersecurity paradigm designed in the lab of computer scientist George Candea that explores challenges to the security and safety of large-scale complex systems, often written by many different programmers. Candea, a Cyberhaven founder, is also the company chairman, with alumni from his lab providing most of the company’s leadership. Cyberhaven says its technology is the result of 7 years of research at EPFL and is protected by 4 patents licensed to the company.

Most businesses and government agencies, says Cyberhaven, rely on enterprise-wide perimeter solutions to ward off hackers, while few executives feel confident about that technology. “Large enterprises and government agencies often deploy antivirus software to satisfy legal obligations or to meet contractual requirements,” says Candea in an EPFL statement, “not because they really believe that the software can defend them.”

The results of a hack on a business can be crippling. The company cites data from IBM estimating the cost of an average breach to an organization at $4 million.

Cyberhaven’s technology tailors security to a business’s workflows, in effect countering the process employed by hackers that prepare malware and intrusions aimed at a company’s specific vulnerabilities, particularly with cloud-based software, such as Office 365 and Google Apps. The company’s process establishes a safe-haven where encryption protects against unauthorized access, but also provides a constant deep analysis of the integrity of data and documents in that workflow. This approach, says the company, can simplify a client’s security infrastructure.

“Instead of building a fortress with many weak walls,” notes Candea, “we protect individual workflows that correspond to users’ activities, such as the preparation of a quarterly financial report or the negotiation of a new inter-governmental agreement. By combining document encryption with Cyberhaven, it will no longer be necessary to use dozens of different security products to protect yourself. This will make your security infrastructure simpler and stronger.”

The company says in a recent third-party test, Cyberhaven’s process caught all 144 attacks prepared by computer security professionals. Other modern solutions, using heuristic analytical methods to anticipate previously unknown methods, stopped 20 of the 144 attacks. Anti-virus software, says the company, stopped just 1.

Cyberhaven was founded in early 2015, and already booked some $640,000 in revenues. The new financing is led by Accomplice, a technology industry venture capital company, joined by other undisclosed industry investors. The funds are expected to support Cyberhaven’s new Cambridge, Massachusetts office, as well as continue its product R&D in Switzerland. The company’s new Cambridge office will be led by co-founder and CEO Vova Kuznetsov, which aims to better position Cyberhaven to serve the large U.S. market.

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Gene Therapy Designed for Muscle Wasting Disease

Adeno-associated virus

Electrostatic image of adeno-associated virus (National Institute of General Medical Sciences, NIH)

28 July 2016. Researchers devised a treatment for a cancer-related muscle wasting disease using gene transfers that in lab mice block cell signals promoting muscle degradation. The team from the Baker IDI Heart and Diabetes Institute in Melbourne, Australia and Washington State University in Pullman, published its findings last week in the journal Science Translational Medicine (paid subscription required).

A research team from the lab of physiologist Paul Gregorevic at the Baker Institute, with colleagues from other institutions in Australia and the U.S., are seeking better treatment options for cancer cachexia, a disorder where cancer in advanced stages encourages deterioration of muscles and weight loss, leading first to fatigue but later to more serious consequences, including heart muscle degradation and death. Some 1.3 million people in the U.S. have cancer cachexia, responsible for 20 percent of all cancer deaths.

Treatments for this and related muscle disorders up to now returned at best mixed results. The degradation of muscle is traced to proteins known as ActRIIB ligands, which can be controlled by another protein, myostatin, responsible for growth and development of skeletal tissues in the body. Preclinical studies and clinical trials with myostatin, however, show the therapy is associated with unwanted adverse effects, including thickening heart muscles and heart failure.

Gregorevic and colleagues are taking a different approach that more precisely targets ActRIIB ligand signals, without the adverse side effects. Their technique increases the output of proteins, expressed by a gene known as Smad7, that prevent only the effects of harmful ActRIIB signals. Proteins expressed by the Smad7 gene block the actions of other proteins in the same genetic family that result from ActRIIB signals.

The team first adjusted the properties of Smad7 genes, then found a way to deliver it. Researchers engineered a form of the Smad7 gene that produces abundant proteins addressing cardiac and skeletal muscle tissue affected by cancer cachexia. To deliver the Smad7 genes, the team used adeno-associated viruses, benign and naturally occurring microbes that can infect cells, but do not integrate with the cell’s genome or cause disease, and generate a mild immune response.

In tests with lab mice, the team delivered Smad7 genes with adeno-associated viruses, which confirmed that proteins from the over-expressing genes block activation of related muscle-wasting proteins from ActRIIB signals. In further tests, mice were induced with colon cancer, and viral-delivered Smad7 genes were shown to prevent muscle wasting in those mice, as well as preserve their muscle mass. No harm was detected to other organs in the mice.

The technology in this study is in early stages of commercialization. Baker Institute and Washington State University filed a patent application for the process. In addition, co-author and animal sciences professor Dan Rodgers at Washington State, who lost his father to cachexia, started the company AAVogen Inc. in 2015 to apply the technology to treatments for a number of muscle diseases.

“I formed this company for one purpose,” says Rodgers in a university statement, “to move the science into society, to see it applied. Now we have a company with the potential to save a lot of lives.”

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