Category Archives: Genetic Engineering

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 companys technology genetically engineers DNA to act as an identifier for the most common drug receptors inside the human genome. Basically, its 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, Octants co-founder and chief executive officer, in a statement.

Octants 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 Kosuris, 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 were 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 hed 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 Octants 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 companys 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 didnt 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 industrys turn away from the big diseases that affect large swaths of the population is that new therapies are emerging to treat these conditions which dont rely on drugs. While they wouldnt 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 $30 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.

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

A scanning electron microscope image showing SARS-CoV-2 (orange), the virus that causes COVID-19, isolated from a patient in the US, emerging from the surface of cells cultured in the lab. Photo and caption: NIAID-RML.

COVID-19 continues to be an immense global challenge, with over 5.2 million confirmed cases and over 338,000 deaths.

In this gloom, science offers hope. Never before have scientists come together to do so much in so little time. Important research that stayed behind paywalls earlier is now openly accessible; over 5,000 articles on preprint servers and over 30,000 viral genome sequences are freely available.

Vaccines against the SARS-CoV-2 virus are also being developed at pandemic speed with 10 candidates in clinical testing and another 114 in pre-clinical development. But the basic understanding of whether a vaccine would work, what might be the correlates of protection, and how would one measure those, has been lacking. This was addressed recently.

Most vaccines in development aim to produce antibodies that would disable the virus from entering target cells. These are produced by B cells. Another arm of immunity utilises T-cells that thwart infection in two ways the helper T-cells help B-cells produce antibodies, and the killer T-cells seek out and destroy virus-infected cells. But a small fraction of virus-specific B, helper-T and killer-T cells also develop into memory cells, which respond very quickly to future infections by the same pathogen.

The success of most COVID-19 vaccines under development rests on whether they can produce neutralising antibodies. How does one measure these antibodies? How long do these take to develop, and how long do they last?

Researchers from Emory University in Atlanta, USA provide answers to some of these questions in a preprint paper posted on the medRxiv server on May 8. Using molecular biology and biochemical tools they obtained purified receptor binding domain (RBD) of the spike protein, which contacts the ACE2 receptors on target cells to facilitate virus entry (see illustration). Antibodies to RBD are expected to neutralise the virus.

The RBD protein was used to develop blood tests to look for anti-RBD antibodies in COVID-19 patients and assess their ability to neutralise the virus in 44 patients. The study showed that RBD-specific and virus-neutralising antibodies correlated nicely and developed very early after SARS-CoV-2 infection. When validated with 231 hospitalised COVID-19 patients, the RBD-specific antibody test was highly sensitive and specific, and found to be a good surrogate for measuring neutralising antibodies.

These findings have important implications for our understanding of protective immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of much-needed vaccines, said Mehul S. Suthar, co-lead author of the study, in an Emory University press release. This study provides a snapshot of the immune response as it is happening, not after the battle is over, he added.

Two recent papers looked at T-cells to SARS-CoV-2. In a paper published May 14, researchers at the La Jolla Institute for Immunology, California, designed peptides (small fragments) corresponding to various SARS-CoV-2 proteins and exposed blood cells from COVID-19 patients to these snippets. Their results showed that all patients carried helper T-cells and over 70% also carried killer T-cells, suggesting that the immune system was seeing the virus and mounting a response. These results agreed well with a study from Charit University Hospital, Berlin, posted on medRxiv on April 22.

These and many other T-cell studies are assisted by the Immune Epitope Database and Analysis Resource and the IEDB website, which is the bread and butter of T-cell epitope mapping.

But the real surprise came when blood cells from people who had no SARS-CoV-2 infection were exposed to these peptides. About a third in the Berlin study and about half in the La Jolla study carried the memory T-cells. These are likely to be from past exposure to one of four other human coronaviruses that are endemic and are estimated to cause 20-30% of common cold annually.

These are comprehensive studies characterising the T-cell response to COVID-19 virus, says Rafi Ahmed, a leading immunologist and director of the Vaccine Centre at Emory University, Atlanta. This information will be useful in designing vaccines that induce T cell immunity against COVID-19, adds Ahmed, who is also a fellow of the US National Academy of Sciences.

Most vaccines under development aim to produce an immune response against the viral spike protein, but the La Jolla study showed the presence of T cells that recognise several other viral proteins. As Ahmed suggests, these studies inform vaccine design by recommending the inclusion of other proteins as well. The whole virus attenuated and killed vaccines may therefore offer better and longer lasting protection compared to single protein vaccines.

Though T-cells are often overlooked and neutralising antibodies are typically considered a correlate to protection, it is well established that poor T cells result in poor memory B-cells and thus long-lived antibodies something all vaccine manufactures and proponents of herd immunity are looking for, says Anmol Chandele, group leader of the ICGEB-Emory Vaccine Programme at the International Centre for Genetic Engineering and Biotechnology, New Delhi.

The blood test developed at Emory University also helps inform vaccine development. Scientists could test the blood of vaccine study participants for the RBD-specific antibodies as a measure of neutralising antibodies, and use it predict vaccine efficacy. The infusion of blood plasma from recovered COVID-19 patients has been proposed as a potential therapy for critical patients. This blood test would also be useful in assessing the therapeutic value of convalescent plasma before infusion.

The Emory University researchers are now using the blood test to assess neutralising antibodies in people who get mild disease or remain asymptomatic. This would inform if such people are at a risk of re-infection. In a pandemic situation, it may also be better placed to offer immunity passports.

Commenting on the Emory study, of which he is an author, Ahmed says, This study makes the important observation that COVID-19 patients rapidly generate neutralising antibodies against the virus. This is a very hopeful sign for protective immunity against re-infection in the recovered patients. This, he says has important implications for public health and for COVID-19 vaccines.

The La Jolla T-cell study links well with the Emory antibody study, where the key result is that RBD-binding antibody titres beautifully correlate to neutralising antibody titres in an individual, adds Chandele, who was not part of either study.

These studies offer hope that vaccine developers will no longer fly blind.

Dr Shahid Jameel is a former Group Leader of Virology at ICGEB, New Dehi, India. He is currently CEO, DBT/Wellcome Trust India Alliance.

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COVID-19 Vaccines: A Reason to Hope We're Flying Blind No More - The Wire

Transhumanists believe humans can and should use technology to artificially augment their capabilities.Natasha Vita-More is Executive Director of Humanity+, formerly the World Transhumanist Association, and is one of the co-authors of the 1998 Transhumanist Declaration.

Speaking toExpress.co.ukshe said: We certainly do need to upgrade our biology and Ive been speaking about this for 30-something years.

The fact that our biology is vulnerable. We exist on a daily basis with an incredible vulnerable vehicle, our bodies, that anything could go wrong at any time.

As far as genetic engineering goes weve seen great work done with certain diseases like Tay-Sachs and sickle-cell anemia, certain cancers, certain diseases that handicap us.

Other gene therapies are in the works and there still needs to be far more work in this area and I think most of us will be undergoing gene therapy as soon as it comes online as needed.

Say 50 years from now I think well be looking at alternative bodies and we can see that really growing in the field of prosthetics.

Transhumanists think human lifespans can be radically extended, with many believing ageing can be reversed and death from disease abolished.

Ms Vita-More argued future humans will look to backup the content of their brains as an insurance policy against death or injury.

She asserted: It is essential our memories be stored some place.

Currently our memories are stored in our brain but thats vulnerable. We have hackers all the time in our brains and those are called viruses and disease.

Disease is constantly hacking our neurons so in order to protect that we need to have copies of it, we need to back it up and you see certain industry leaders like Google looking at how to back up the brain.

I see uploading as a necessary technology for not only backing up the brain but as a means for us to go into different environments.

Were currently in this physical/material world, this biosphere, there are other worlds yet to be explored just as were looking at space exploration.

READ MORE:Oxford academic claims future humans could live for thousands of years

Another area is virtual reality, augmented reality, all these other systems even in games to go into games and participate as yourself taking on an avatar or maybe something else.

Asked about those who might object, on religious or moral grounds, to radical life extension Ms Vita-More expressed confidence their arguments would be overcome.

She commented: I think its largely religious but I think it is also innate.

I think the narrative is engrained in culturalization, it seems to be endemic across cultures.

Given that plus the largest percentage of people on our planet are religious that puts a damper on it too. However it doesnt prevent it.

It could be interesting if we see religious doctrines changing a little bit to include life extension and changing as weve seen with divorce.

If you believe an afterlife it doesnt have to happen at exactly a certain time. Maybe instead of 90 as a lifespan maybe 300 if you want to go that route.

So well see a realisation that religions have to keep up with the state of society and their members within that.

Ms Vita-More is also an advisor to the Singularity University and co-editor and contributing author to The Transhumanist Reader: Classical and Contemporary Essays on the Science, Technology, and Philosophy of the Human Future.

Asked what most excites her about the future she replied: I would like to totally reengineer my body, its not available yet but Id like to have a whole new body thats smoothly integrated not only with narrow artificial intelligence (AI) but with artificial general intelligence and Id like to have a metabrain where Id have AI working with me like a best friend or cohort.

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Humans will be able to replace their bodies within 50 years claims transhumanist writer - Express.co.uk

There is no silver bullet to the ability to feed a global population of more than 9 billion people by 2050. There is a menu of solutions across many sectors of the food economy, according to Jack Bobo, CEO of food consultancy firm Futurity, who spoke May 21 during Alltechs ONE Virtual Experience.

When it comes to sustainability, the ideas of local sustainability vs. global sustainability are often very different from each other, Bobo said.

When we think about local sustainability, thats really how most consumers think about sustainability, because theyre thinking about farmers using less fertilizer and less insecticide and producing things in a way that doesnt have runoff into the local environment, he said. They want to have less of an impact of agriculture on the land.

But, he pointed out, methods such as organic agriculture result in 20-30% less food for a given amount of land.

Imagine for a moment that the entire world were organic: What would that mean? he asked. Well, the main thing it would mean is that we just wouldnt have any forest anymore, because we would need 20% to 30% more land in order to produce the food we have. And 40% of all the land on earth is already used for agriculture. So that would have a devastating impact.

For this reason, the concept of global sustainability is the opposite of local sustainability.

Its about prioritizing intensive agriculture in one place in order to protect the environment somewhere else, he said. That could mean more intensive livestock production through contained animal feeding where you see the environmental impact locally of that intensive agricultural production. But what you dont see is that you dont need to have more animals going out into in Brazil, where they have to cut down forests in order to make way for expanded livestock production. So, you dont see the land protected; you only see the local impact. This comparison between local and global sustainability is part of the different story that were telling.

But, Bobo said we need local and global sustainability; neither one is right or wrong.

Its really about choices and consequences, he said. But there are consequences to the choices we make.

Those choices the menu of solutions will be different across various regions or sectors, and they will all work together to create a better food production system to feed the world.

Rather than thinking about sustainability as farming is the problem, I like to think that Im just happy that consumers and conservationists are now joining farmers on this journey of sustainability, because we could use their help, he said. And instead of framing it as agriculture is the problem to be solved, we need to help them to understand that agriculture is the solution to the problem.

Some of the solutions Bobo discussed include:

Shifting diets: For many, if we would all just become vegan or vegetarian, we wouldnt have any problems, he said.

But, while there is a need for a healthier diet in the developed world, in low-income regions, people eat more protein as their income increases.

So, even if we do shift diets in the United States and Europe and places like that, people are going to be shifting their diets in a way that increases the impact of agriculture in most places around the world, he said.

Food waste: One-third of all the food produced is lost to food waste, Bobo said. The good news is that people are much more focused on this issue than they were 20 years ago. But, in the developed world, that waste is post-consumer whereas in the developing world, the waste happens along the supply chain.

Addressing food waste is hard, because food waste is not one problem. Food waste is a thousand problems, he said. Food waste doesnt just occur in the field. It doesnt just occur in storage. It doesnt just occur during distribution. It occurs at all of these different points along the supply chain.

Cover crops: While organic farmers have advocated for cover crops for decades, big data has shown a return on investment that has larger farmers also adopting this low-tech solution.

Cover crops are adding some nutrients theyre reducing soil erosion, he said.

Gene editing and genetic engineering: These are more high-tech solutions to increasing crop production and lowering environmental impact. Plants can be genetically engineered to be resistant to insect damage or be more tolerant to drought, for example.

There are all sorts of solutions to the problems of agriculture. And they occur, whether its organic, high tech, or otherwise, he said.

Alternative proteins: Whether its companies that create alternative proteins through fermentation, cellular technology or plant-based products, they are all competing for market share instead of working together toward a solution.

When we think about trying to feed the world in 2050, the market opportunity is $1 trillion dollars just in the protein space, he said. Who really believes that plant-based meat is going to become a trillion-dollar industry in just 30 years? And even if, somehow, they did become a trillion-dollar industry, so what? We wouldnt lose a single cow, we wouldnt lose any cattle. Wed still be producing all of that food in the same way that we did, and hopefully, in a much, much more environmentally friendly way.

More here:
Menu of solutions, no silver bullet, to feed the world - FeedStrategy.com

New Delhi | Updated: May 22, 2020 3:16:36 pm

Written by Dr R L Raina

With the Indian government keen on promoting India as a medical tourist destination for patients seeking affordable treatment, there is going to be a demand for healthcare professionals. To meet this demand, a new course on healthcare engineering has emerged for students. It is a multi-disciplinary specialty that focuses on advancing this sector through engineering approaches involving both healthcare and engineering professionals.

In this course, candidates will not only need to know their subject, but also possess entrepreneurial skills, along with business and technology acumen. Researchers work with clinicians, collaborators and patients to identify and solve problems that are relevant today. They use scientific, engineering methodology to create solutions to complex health care problems and improve quality of life.

Read| Emerging courses to pursue:Virology|Actuarial science| Pharma Marketing|FinTech|Coronavirus|Robotics | Healthcare Engineering | Cyber Security | Data Science

As a healthcare engineer, one needs to have the knowledge of engineering principles that will enable him/her to come up with solutions for healthcare. At times, it is also concerned with the development and design of a medical product. Some of the major skills that an aspirant requires:

Analytical skills Good eye for design Vast knowledge about various diseases Attention to detailing Communication

To pursue a Bachelors degree in healthcare engineering, a candidate must have cleared class 12 exams, with science subjects like biology, mathematics, physics, and chemistry. The course curriculum will be around the application of engineering tools in the healthcare industry and developing new cutting edge equipment to protect people from illness and injury, and property from damage.

Read |Colleges offering AI-powered exams from home: All you need to know about proctoring

Engineers are always in demand in healthcare. It is a misconception that only people who have studied biomedical and clinical engineering can become healthcare engineers. Even students pursuing chemical, civil, computer, electrical, environmental, industrial, information, materials, mechanical, software and systems engineering can pursue this field.

Biomechanics: It is the study of the structure, function and motion of the mechanical aspects of biological systems by using the methods of mechanics.

Medical devices: Under this, a student should have knowledge about devices that benefit patients by helping healthcare providers diagnose and treat patients and helping them overcome sickness or disease, improving their quality of life.

Genetic engineering: It is the knowledge of a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms.

Read |IIT-Gandhinagar launches PG courses, direct admission for students affected by coronavirus

Health Informatics: This is the study of a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms.

Emergency Management: According to the World Health Organisation (WHO), emergency is a state in which normal procedures are interrupted, and immediate measures need to be taken to prevent that state from turning into a disaster. Thus, emergency management is crucial to avoid the disruption transforming into a disaster, which is even harder to recover from.

If you are interested in public health challenges, this is the perfect time to pursue a career in healthcare engineering. It is in high demand as they have a crucial role to play in terms of designing and validating models in the context of public health, predictive modelling, epidemiological studies, machine learning and data visualisation. These skills are already some of the most sought after across a wide variety of sectors, and healthcare has also caught up during the current crisis.

Healthcare engineering covers the following two major fields:

Engineering for Healthcare Intervention: This comes into play when there are chances of any treatment, preventive care, or test that a person could take or undergo to improve health or to help with a particular health problem.

Read | How will colleges function post lockdown

Engineering for Healthcare Systems: Engineering involved in the complete network of organisations, agencies, facilities, information systems, management systems, financing mechanisms, logistics, and all trained personnel engaged in delivering healthcare within a geographical area.

Universities offering this course

Since it is a relatively new course in India, none of the Indian universities offer this course yet, but some international universities do, such as Texas Tech University, Cambridge University, and John Hopkins University.

The author is vice-chancellor, JK Lakshmipat University

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Emerging courses: How to become a healthcare engineer - The Indian Express

Any Italian will tell you that the north and south are poles apart, and it appears those differences may have begun as many as 20,000 years ago.

New research suggests that genetic adaptions to environmental changes, such as those that occurred soon after the Last Glacial Maximum, could explain some of the genetic differences between northern and southern Italian populations today.

A team from the University of Bologna sequenced the genomes of 38 unrelated participants from different regions in Italy, each the third generation of their family native to each region.

The genomes were selected as representative of known genetic differences across the Italian population and over 17 million distinct genetic variants were found between individuals.

Marco Sazzini and colleagues then compared these variations with existing genetic data from 35 populations across Europe and the Mediterranean and with variants previously observed in 559 ancient human remains, dating from the Upper Palaeolithic (around 40,000 years ago) to the Bronze Age (4000 years ago).

When comparing sequences between modern and ancient genome samples, we found early genetic divergence between the ancestors of northern and southern Italian groups dating back to the Late Glacial, around 19,000-12,000 years ago, Sazzini says.

Migrations during the Neolithic and Bronze Age periods, thousands of years later, then further differentiated their gene pools.

Divergence between these ancestral populations may have occurred as a result of temperature rises and subsequent shrinking of glaciers across northern Italy during this time, allowing ancestors who survived the glaciation period to move north, separating from groups who remained in the south.

The researchers note, however, that they are unable to prove causation or to rule out the possibility that more recent gene flow from populations exposed to diverse environmental conditions outside of Italy may have also contributed to the different genetic signatures.

Writing in the journal BMC Biology, they say their analyses reveal signatures ascribable to specific biological adaptations in northern and southern Italian genomes suggestive of habitation in differing climates.

The genetic history of northern Italians shows changes in the genes responsible for regulating insulin, body-heat production and fat metabolism, while southern Italians showed adaptations in genes regulating the production of melanin and responses to pathogens.

Our findings suggest that the ancestors of northern Italians adapted to lower environmental temperatures and the related high-calorie diets by optimising their energy metabolism, Sazzini says.

This adaptation may play a role in the lower prevalence of Type 2 Diabetes recorded in northern Italy today. Conversely, southern Italian ancestors adapted to a warmer climate with higher UV levels by increasing melanin production, which may explain the lower incidence rates of skin cancers recorded across southern regions.

The genomes of southern Italians also showed changes in the genes encoding mucins, which play a role in protection against pathogens, and genetic variants linked to a longer lifespan.

Read more:
Why Italians aren't all the same - Cosmos

There is "no evidence" supporting conspiracy theories that the coronavirus originated in a laboratory in Wuhan, an expert has told parliament.

Claims that COVID-19 was created in a lab were amplified by Donald Trump earlier this month, although the president refused to offer any evidence or give specific details.

The coronavirus outbreak first emerged in the Chinese city of Wuhan last year and international blame around the pandemic has incited conspiracy theories about its origin.

Rumours linking the virus to the Wuhan Institute of Virology - based on geographic proximity, and without any endorsement from qualified epidemiologists - have circulated.

But speaking to the House of Lords science and technology committee on Tuesday, Professor David Robertson dismissed the conspiracy theory as "unlikely".

Following the president's comments, the US Secretary of State Mike Pompeo claimed there was a "significant amount of evidence" supporting the theory but, just two days later, admitted: "We don't have certainty."

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Scientists have discovered that the coronavirus was 96% identical to coronavirus found in bats, one of the many animals sold at a Wuhan seafood market where it is suspected the virus jumped to humans.

British authorities believe it is highly likely the global pandemic is unconnected to the laboratory in Wuhan and was passed from animals to humans naturally.

"You have a virus that you think comes from an exotic species and then you have a wildlife market - that seems the most parsimonious explanation," Professor Robertson said.

He was asked whether a sample of the virus found at the Wuhan Institute of Virology - and thought to be about 40 to 50 years old - could have been behind the initial outbreak.

Professor Robertson, who is the head of viral genomics and bioinformatics at the University of Glasgow, firmly responded: "No, absolutely not.

"That's partly what has driven some of these conspiracy theories, is what is the chance they would have this virus in the labs that is close? And actually, even though it is close in sequence, it is not close in time."

"There is really no evidence for this. We can all enjoy a conspiracy theory but you need to have evidence," he added.

Scientists have analysed the entirety of the novel coronavirus' genomic sequence to assess claims that it may have been made in a laboratory or been otherwise engineered.

The value of the genomic sequence could prove vital for those developing a vaccine, but it also contains key details revealing how the virus evolved.

Researchers at the Scripps Research Institute in the US, UK and Australia discovered that the virus has proved so infectious because it developed a near-perfect mechanism to bind to human cells.

This mechanism is so sophisticated in its adaptions that the researchers say that it must have evolved and not been genetically engineered in their paper, titled "COVID-19 coronavirus epidemic has a natural origin", published in the journal Nature Medicine.

Dr Josie Golding, the epidemics lead at the Wellcome Trust in the UK, described the paper as "crucially important to bring an evidence-based view to the rumours that have been circulating about the origins of the virus causing COVID-19".

"They conclude that the virus is the product of natural evolution, ending any speculation about deliberate genetic engineering," Dr Golding added.

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Coronavirus: Parliament told there is 'no evidence' virus came from Wuhan laboratory - Sky News

From a purely chemical standpoint, a cannabinoid is a cannabinoid and a THC molecule is a THC molecule, no matter how its produced, whether in a lab or grown on a farm. From a legal perspective, a cannabinoid is a cannabinoidat least in Canada. Production and distribution of CBD is held to the same standards as the psychoactive compounds in cannabis.

However, in the US, THC and CBD are legally distinct. After the 2018 Farm Bill passed, hemp and cannabis with extremely low percentages of THCless than 0.3%became federally legal. So while non-psychoactive cannabinoids may act, look, and quack like ducks, they might turn out to be swans.

This possibility has researchers and companies salivating at the medical possibilities and potential profits of the less common cannabinoids contained in cannabis plants. These rarer cannabinoids appear at such low levels that its impractical to extract large quantities from marijuana plants. But a little genetic engineering, a lot of research, and a few metal tanks full of yeast bacteria could make mass-production possible.

Yeast fermentation is an age-old process, familiar to most as a source of beer or bread. But in the scientific community, its known as one of the primary bacteria used to produce biopharmaceuticals (the other is E. coli).

Today, the scientific race is on to study specific cannabinoids other than THC or CBD as treatments for illnesses such as epilepsy. And the commercial race is on to provide those cannabinoids to research institutions.

From a researchers perspective, it doesnt matter how the cannabinoid is produced. Consistency and reliability of supply are required, not sunlight and dirt. While yeast has to be genetically modified to produce a cannabinoid, the end product is genetically identical to its plant-produced counterpart.

While there is no safety or efficacy concern, from a consumer perspective, substance origin can matterif you know about it. But once cannabinoids have been harvested and refined into an oil, its impossible to tell whether they came from a plant or a test tube. They all quack like ducks.

Theres so much territory to explore. Were just taking the first steps, said Cynthia Bryant, the Chief Business Officer at Demetrix, a US company focusing on the potential medical benefits of non-psychoactive cannabinoids for the US pharmaceutical market.

Based out of California, Demetrix is working toward large-scale, non-farming cannabinoid production. And they think yeast fermentation will take them there.

The technology works very well to produce a rare cannabinoid, said Bryant. Once they are up and running, they will be able to quickly and regularly produce large amounts of specific cannabinoids, setting up a supply chain thats reliable enough for pharmaceutical research and medicines. Sales could include oils and crystalized powders for research, clinical trials, and eventually, as active ingredients in medications.

Over a hundred different cannabinoids can be extracted from cannabis plants, but many exist at such low levels that they have never been studied as isolated medical ingredients.

Demetrix has identified the first so-called rare cannabinoid that they want to bring to market. Bryant wouldnt name the specific cannabinoid the company plans to release to market next year, citing trade secrets, and said only that theyve discovered some useful effects.

Insulin, the first biopharmaceutical, was once extracted from pig pancreases. In the late 1970s scientists cloned the gene that makes the human body produce insulin, cut out a piece of DNA from a yeast cell, and inserted the engineered gene into its place. Instead of producing alcohol, the yeast cells became tiny factories that produced insulin.

Suddenly, it was exponentially easier and cheaper to manufacture insulin. The new method was fast, consistent, and scalable, allowing it to be replicated at commercial levels. It is also completely safe. Todays yeast fermentation process is similar, if significantly advanced.

Demetrix mail orders synthetically produced DNA sequences of the enzymes in cannabis that have been identified as instigators of natural cannabinoid production. Scientists then insert the DNA sequence into yeast cells, reprogramming their purpose. The specific methods used to do this vary from company to company and are considered trade secrets. But the general tack of using a microorganism to produce a specific molecule is common across the field.

The modified yeast cultures are then left to ferment and grow in tanks, multiplying and producing large amounts of the desired cannabinoid. Workers then extract the cannabinoids from the yeast slurry, isolate, and purify them.

I think theres going to be a huge need for these cannabinoids, said Bryant. The more cannabinoids are studied, the more medical solutions might be found. So its a good thing that the fermentation field is crowdedand that cannabinoid plant extraction is also plowing forward, Bryant explained. Competition will bring down prices and increase availability, she said. We need all of the various sources.

Far north of Demetrixs Berkeley, CA, base, Canadian company Hyasynth is just about ready for full-scale production of fermented cannabinoids, said Kevin Chen, Hyasynths CEO.

Hyasynth also mail orders DNA sequences, slots them into yeast genomes, and extracts the desired compounds from the slurry to produce medical grade cannabinoids for sale to pharmaceutical companies.

Its the modern way, said Chen, who extolled the same virtues of fermentation over farming as Demetrix does: scale, consistency, speed, and, most especially, specificity. We have full control over which cannabinoid we produce and which we dont.

Fermentation is a process that takes five days, instead of the three months it would take to plant and grow marijuana to use for enzyme extraction, he said. Farming can be difficult. Once you nail down your specific splicing method, fermentation is easy.

Engineered cannabinoids may be superior for pharmaceutical purposes, but not everyone will want cannabis grown in tanks or tubes, Chen acknowledges.

Were not too worried about people rejecting our product, said Chen. Were using yeast to manufacture things, but the yeast isnt what were selling.

From the standpoint of personal preference, not all cannabinoids are equal. Some consumers might prefer a holistic, whole-plant product. Some might only care about results.

Do people care that it comes from a different place? Absolutely, said Chen. But different methods of cannabinoid production are suited to different purposes, and fermentation seems poised to win in a pharmaceutical ingredient contest. It is differentin many ways its better.

Celia Gorman is a science journalist and video editor based out of New York. She holds a master's in digital journalism from the CUNY Graduate School of Journalism and previously worked as an Associate Editor at tech magazine IEEE Spectrum, where she developed and ran an award-winning video section.

Original post:
Yeast fermentation may be the answer to creating rare cannabinoids - Leafly

Walking towards the school gate, as I adjusted the N-99 face mask on my four-year-old, I felt deeply disturbed. The AQI numbers in our city had soared to hazardous levels and the air pollution was causing worrisome adverse effects on the tiny lungs of our children.

Pollution was not the only cause for anxiety. The extreme weather conditions, the rise of vector-borne diseases like dengue and chikungunya, the continuing emergence of novel viruses, the increasing resistance of infectious agents to medication: everything was pointing towards an extremely grim future in the world of health. The thought of our children being the bearers of such a future perplexed me, both as a mother and as a pulmonologist.

Thus started my exploration of the obvious, yet oft-ignored, changes taking place in our ecosystems and led me to my research on climate change.

The AQI numbers in our city had soared to hazardous levels and the air pollution was causing worrisome adverse effects on the tiny lungs of our children. (Photo: Reuters)

The direct effects of climate change on our health are easy to guess. The average global temperature of the earth, which has increased by 1C since the pre-industrial era, is rising at a rate of 0.2C per decade. It may soon reach a level that is irreversible (2.5C above the pre-industrial average). 95 per cent of this global warming is being caused by greenhouse gases, the atmospheric levels of which are increasing alarmingly due to human activities. This global warming is causing melting of ice masses, the rise of sea levels and major alterations in regional precipitation patterns, resulting in unprecedented and extreme weather conditions heatwaves, wildfires, earthquakes, floods, tsunamis and snow-storms. These natural calamities are leading to deaths, diseases, malnutritionand mental health issues. Extreme temperatures are causing heat strokes, respiratory and cardiovascular diseases. Greenhouse effects are leading to diseases because of air pollution.

But what is more important and less obvious is the gradual and persistent damage that is being caused by climate change to the natural habitats and ecosystems of the world, and its quietyet devastating effects on our health.Think about it why are we having newer and frequent viral infections to deal with? Why are our children falling sick so often? Why is every simple viral cough leading to bronchitis? Why is the prescription of anti-inflammatory inhalers, medicines that were reserved for asthmatics, increasing rampantly?

Climate change, human behaviour and emerging infections

75 per cent of emerging infectious diseases, like Influenza, HIV/AIDS, Ebola, SARSand MERS are zoonotic. It means that they exist in animals but can be transmitted to humans.Most of them are caused by viruses predominantly RNA viruses.

Loss of Biodiversity: Climate change and land loss cause loss of habitat, leading to extinction or relocation of native species, with growing predominance of invasive, resilient species. These become likely to harbour and transmit pathogens (so-called reservoir hosts). In a healthy ecosystem, where biodiversity is high, multiple species dilute the effect of the reservoir species, the so-called dilution effect. Studies on hantavirus, West Nile virus etc. have shown strong links between low biodiversity and high rates of viral transmission.

The average global temperature of the earth, which has increased by 1C since the pre-industrial era, is rising at a rate of 0.2C per decade. (Photo: Reuters)

Migration of species: Global warming causes many species to migrate away from the equator and toward higher altitudes, bringing them in contact with new pathogens, to which they have not evolved resistance. These animals are also stressed and immunosuppressed, hence more susceptible to infection.

Contact with humans: Disruption of pristine forests by anthropogenic activities like mining,road building, urbanisation and livestock ranching brings people into closer contact with forest species, increasing the interaction between them. Ebola fever has had several outbreaks in Africa since 1970 because of increased interaction of local population with fruit bats due to population growth and encroachment into forest areas. Kyasanur forest disease, once limited to Karnataka, has spread to adjacent states over the last five years, because of conversion of forests into plantations and paddy fields, that has brought the locals nearer to monkeys.

Intermediate hosts and inter-species transmission: Although most of the novel viruses, including SARS-CoV-2, are generalist viruses that infect many different hosts, jumping into human species from wildlife species is not easy because of significant biological barriers. Transmission from mammalian species which are genetically closer to humans (the intermediate hosts), like pigs, is easier. Pig farming around forests facilitated the transmission of Nipah virus from bats in Malaysia, and civet cats sold in wet markets transmitted SARS-CoV from bats in China.

The market connection: In informal wet markets, animals are slaughtered, cut up and sold on the spot. The Wuhan wet market soldnumerous wild animals - live pangolins, wolf pups, crocodiles, foxes, civets. Wet markets in Africa sell monkeys, bats, birds, etc. They are a perfect platform for cross-species transmission of pathogens as novel interactions with a range of species occur in one place. 39per cent of the early cases in the SARS outbreak were wildlife food handlers, likely connected to the wet market of Guangdong, China.

The Wuhan wet market sold numerous wild animals, making it a perfect platform for cross-species transmission of pathogens.

Human transmission: Once inside new hosts, most viruses, fortunately, adapt, replicate and transmit inefficiently. Out of the 1,399 recognised human pathogens, 500 are transmissible between humans, and only 100to 150 are sufficiently transmissible to cause epidemics or pandemics. Restrictions occur at many cellular levels like entry into host cells by receptor binding, trafficking within cell, genome replication and gene expression. Each barrier requires a corresponding genetic change or mutation in the virus. RNA viruses, especially single-stranded RNA viruses like coronavirus, replicate rapidly and are prone to mutations due to lack of a proofreading mechanism. Only after extensive replications and re-assortments in the genome of H3N2 influenza A virus, was it capable of causing the 1968 pandemic.

Human behavioural changes: Factors like international travel, international trade of wildlife, urbanisation, and increase in population density further facilitate transmission.

Covid-19: What do we know?

In late December 2019, Wuhan Centre for Disease Control and Prevention detected a novel coronavirus in two hospital patients with atypical pneumonia. It sent the samples to the Wuhan Institute of Virology for further investigation. The genomic sequence of the virus, eventually named SARS-CoV-2, was 96 per cent identical to that of a coronavirus identified in horseshoe bats in a bat-cave in Yunnan during virus-hunting expeditions. It belonged to the SARS group of coronaviruses.

The expeditions were carried out by the Director of the Centre for Emerging Infectious Diseases at the Wuhan Laboratory, Shi Zhengli (nicknamed Chinas Bat-woman) and her team, from 2004 for over 16 years, in an attempt to isolate the SARS coronavirus. They discovered hundreds of bat-borne coronaviruses with incredible genetic diversity in bat-caves deep inside forests. In bat dwellings, constant mixing of different viruses creates a great opportunity for dangerous new pathogens to emerge and the bats turn into flying factories of new viruses.

But bats were not present at the Wuhan wet market. The wild pangolin, sold for its exotic meat and medicinal scales, became suspect as an intermediate host when a SARS-CoV-2 like coronavirus was discovered in pangolins that were seized in illegal trade markets in southern China.

Whether or not the SARS-CoV-2 was accidentally or deliberately released from the Wuhan Laboratory is a debate not proven. None of the coronaviruses that were under study in this laboratory were identical to the SARS-CoV-2 virus. Also, researchers believe that the spike proteins present on the viral surface, that target the ACE2 receptors on human cells, are so effective in binding the virus to the cells, that they could have developed only by natural selection and not by genetic engineering. When computer simulations were carried out, the mutations in the SARS-CoV-2 genome did not work well in binding the virus to human cells, leading to the argument that if scientists were to deliberately engineer the virus, they would not choose mutations that computer models suggested did not work.

A recent analysis done in China estimates that there are now more than 30 strains of the virus spread across the globe.(Photo: Reuters)

Whatever the origin of the virus, the response to develop what is needed to control the present outbreak remains the same, as do the policies needed to prevent such outbreaks in the future.

A recent analysis done in China estimates that there are now more than 30 strains of the virus spread across the globe. This means that it has already mutated 30 times, which filters down to roughly one mutation every two weeks. More studies are needed to determine the effects of these mutations on the virulence and transmissibility of the virus. But going by the rapidity with which Covid is taking over the world, it should be an easy guess.

So really, is the Covid-19 pandemic a surprise? Not at all. It was coming, and so will others.

Covid-19 has thrown us into a world of turmoil and uncertainty. The impacts on health and economy have been devastating. The only thing that is flourishing is nature! Maybe nature will make us see what innumerable climate-related world conferences could not. It is there for us to appreciate in its full glory the blue skies, the clean air, the blooming flowers, the variety of birds and the wild creatures returning to claim the land that was once theirs. Nature is sending us a message. It would do us good to heed to it.

Also read| I don't believe you: Donald Trump, world's biggest climate change denier

Here is the original post:
Climate change and coronavirus: Is the Covid-19 pandemic really a surprise? - DailyO

XconomyBoston

Gene therapies deliver healthy genetic material to patients cells to replace a mutated, disease-causing variant. Dyno Therapeutics aims to create better delivery vehicles for those genes by using machine-learning tools to engineer new types of harmless viruses that are more effective and simpler to manufacture.

The Cambridge, MA-based biotech emerged from stealth Monday having signed deals with two drug makers who want to apply its technology to their gene therapy effortsagreements its founders say are lucrative enough to fund the company for years to come. Dyno spun out of George Churchs lab at Harvard Medical School in late 2018 with $9 million in seed funding from Polaris Partners and CRV.

Now Dyno has signed collaboration agreements with Novartis (NYSE: NVS) and Sarepta Therapeutics (NASDAQ: SRPT) to design superior versions of the adeno-associated viruses, or AAVs, commonly used in gene therapies, and the company says the deals may preclude it from needing to raise outside funds again. Thats a rarity for a biotech that is already considering advancing its own product candidates in addition to striking R&D arrangements with other biotechs and pharmaceutical companies.

The first gene therapy in the US was approved in 2017. Finding better AAVs in which to insert genetic material has proven challenging because tweaking the complex protein shells to improve one property, such as targeted delivery, can impede others, such as their ability to evade the immune system.

With small molecules and antibodies, the drug is the small molecule or the antibody, and sometimes youll require a delivery system but thats not the important part, Polaris partner Alan Crane, one of Dynos founders, said in an interview. Its almost flipped in gene therapy, because everyone knows what gene to deliver, generally, for a particular disease, but they dont know how to deliver it, and we really need these better vectors.

Dyno will work with Novartis to use its CapsidMap platform to design superior AAV vectors for gene therapies for eye diseases; Sareptas area of interest is muscle disease.

Under the terms of the deals, the larger companies will be responsible for taking any gene therapy product candidates created within the collaborations through preclinical and clinical testing and commercialization. In the Novartis agreement, Dyno gets an undisclosed amount of money up front plus research funding and license fees. If any products advance, it will be eligible for payments tied to clinical, regulatory, and sales milestones, plus royalties on sales.

In the Sarepta agreement, during the research phase of the collaboration, Dyno will be eligible for more than $40 million in payments. If candidates are developed, it will be eligible for additional payments tied to development milestones, plus royalties. The company wouldnt disclose additional financial details, but said if everything goes according to plan, the deals it has struck to date could collectively bring the startup more than $2 billion.

CEO Eric Kelsic said that when he joined Churchs lab, he aimed to use his experimental and computational biology background to combine the latest technologies in high-throughput biology, advanced machine learning, and protein engineering. He was exposed to gene therapy through Churchs work with the gene editing technology CRISPR-Cas9, one of the tools being deployed to address genetic diseases.

It just seemed like the perfect application of the technologies we had been working on, which are certainly going to transform all of protein engineering, Kelsic said in an interview.

The company takes available data, plus more it generates itself using high-throughput measurement technologies, and uses it to build machine-learning models that suss out the most optimal synthetic capsids. Using machine learning allows Dyno to take into account a number of important propertiesdelivery, immunity, packaging size, and manufacturing, for examplewhile weighting those most important to the particular disease indication. Thats compared to todays efforts, which generally can only tweak one property at a time.

Its been the case in the past that when you only select for one property, for example the efficiency of delivery, that might be improved, but the manufacturability might actually get more challenging, Kelsic said. Thats a tradeoff which has really limited engineering efforts in this space, but now we can overcome that using our platform, optimizing for both the efficiency and the manufacturability and so on, across all the different properties that are important.

Machine-learning tools also allow each experiment to build upon the findings of previous iterations.

When Crane and Kelsic first met, in June 2018, the scientist presented the investor with a spreadsheet of companies that were interested in what the startup had developed. That was before Dyno had published any of its results.

Before joining Polaris in 2002, Crane headed corporate development at Millennium Pharmaceuticals. (Takeda Pharmaceutical (NYSE: TAK) acquired Millennium in 2008 for $8.8 billion). Since joining the VC firm in 2002, Crane has been founder, chairman, or CEO of seven of the companies it has started.

We and a lot of folks in the VC world have been looking at AI applications to healthcare, and increasingly to life sciences and biology, but this was by far the best application to biology that I have ever seen, Crane said. Ive seen a lot of business development, and Ive never seen such robust interest in a young company platform.

Crane says Dyno is currently in talks with other companies that will likely lead to one or two more partnerships like those it has struck with Novartis and Sarepta. The company says it wont allow any company to use its tech to explore a certain disease area exclusively so that it can potentially be used across the industry. In addition to eye and muscle diseases, company is also looking at how to design better vectors for disorders of the central nervous system and the liver.

Along with Kelsic, Church, and Crane, Dynos co-founders are Sam Sinai, its lead machine learning scientist, Adrian Veres, and Tomas Bjorklund.

Sarah de Crescenzo is an Xconomy editor based in San Diego. You can reach her at sdecrescenzo@xconomy.com.

Link:
Dyno Debuts With Plan, Partnerships For Better Gene Therapy Vectors - Xconomy