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Cell Biology

Bit Bios enter button for the keyboard to the software of life nabs the company $41.5 million – TechCrunch

Bit Bio, the new startup that pitches itself as the enter button for the keyboard to the software of life, only needed three weeks to raise its latest $41.5 million round of funding.

Originally known as Elpis Biotechnology and named for the Greek goddess of hope, the Cambridge, England-based company was founded by Mark Kotter in 2016 to commercialize technology that can reduce the cost and increase the production capacity for human cell lines. These cells can be used in targeted gene therapies and as a method to accelerate drug discovery at pharmaceutical companies.

The companys goal is to be able to reproduce every human cell type.

Were just at a very crucial time in biology and medicine and the bottleneck that has become really clear is a scalable source of robust human cells, said Kotter. For drug discovery this is important. When you look at failure rates in clinical trials theyre at an all-time high thats in direct contradiction to the massive advancements in biotechnology in research and the field.

In the 17 years since scientists completely mapped the human genome, and eight years since scientists began using the gene editing technology known as CRISPR to edit genetic material, theres been an explosion of treatments based on individual patients genetic material and new drugs developed to more precisely target the mechanisms that pathogens use to spread through organisms.

These treatments and the small molecule drugs being created to stop the spread of pathogens or reduce the effects of disease require significant testing before coming to market and Bit Bios founder thinks his company can both reduce the time to market and offer new treatments for patients.

Its a thesis that had investors like the famous serial biotech entrepreneur, Richard Klausner, who served as the former director of the National Cancer Institute and founder of revolutionary biotech companies like Lyell Immunopharma, Juno and Grail, leaping at the chance to invest in Bit Bios business, according to Kotter.

Joining Klausner are the famous biotech investment firms Foresite Capital, Blueyard Capital and Arch Venture Partners.

Bit Bio is based on beautiful science. The companys technology has the potential to bring the long-awaited precision and reliability of engineering to the application of stem cells, said Klausner in a statement. Bit Bios approach represents a paradigm shift in biology that will enable a new generation of cell therapies, improving the lives of millions.

Photo: Andrew Brookes/Getty Images

Kotters own path to develop the technology which lies at the heart of Bit Bios business began a decade ago in a laboratory in Cambridge University. It was there that he began research building on the revolutionary discoveries of Shinya Yamanaka, which enabled scientists to transform human adult cells into embryonic stem cells.

What we did is what Yamanaka did. We turned everything upside down. We want to know how each cell is defined and once we know that we can flip the switch, said Kotter. We find out which transcription factors code for a single cell and we turn it on.

Kotter said the technology is like uploading a new program into the embryonic stem cell.

Although the company is still in its early days, it has managed to attract a few key customers and launch a sister company based on the technology. That company, Meatable, is using the same process to make lab-grown pork.

Meatable is the earliest claimant to a commercially viable, patented process for manufacturing meat cells without the need to kill an animal as a prerequisite for cell differentiation and growth.

Other companies have relied on fetal bovine serum or Chinese hamster ovaries to stimulate cell division and production, but Meatablesays it has developed a processwhere it can sample tissue from an animal, revert that tissue to a pluripotent stem cell, then culture that cell sample into muscle and fat to produce the pork products that palates around the world crave.

We know which DNA sequence is responsible for moving an early-stage cell to a muscle cell, says Meatable chief executive Krijn De Nood.

If that sounds similar to Bit Bio, thats because its the same tech just used to make animal instead of human cells.

Image: PASIEKA/SCIENCE PHOTO LIBRARY/Getty Images

If Meatable is one way to commercialize the cell differentiation technology, Bit Bios partnership with the drug development company Charles River Laboratories is another.

We actually do have a revenue-generating business side using human cells for research and drug discovery. We have a partnership with Charles River Laboratories, the large preclinical contract research organization, Kotter said. That partnership is where we have given early access to our technology to Charles River They have their own usual business clients who want them to help with their drug discovery. The big bottleneck at the moment is access to human cells.

Drug trials fail because the treatments developed either are toxic or dont work in humans. The difference is that most experiments to prove how effective the treatments are rely on animal testing before making the leap to human trials, Kotter said.

The company is also preparing to develop its own cell therapies, according to Kotter. There, the biggest selling point is the increased precision that Bit Bio can bring to precision medicine, said Kotter. If you look at these cell therapies at the moment you get mixed bags of cells. There are some that work and some that have dangerous side effects. We think we can be precise [and] safety is the biggest thing at this point.

The company claims that it can produce cell lines in less than a week with 100 percent purity, versus the mixed bags from other companies cell cultures.

Our moonshot goal is to develop a platform capable of producing every human cell type. This is possible once we understand the genes governing human cell behaviour, which ultimately form the operating system of life, Kotter said in a statement. This will unlock a new generation of cell and tissue therapies for tackling cancer, neurodegenerative disorders and autoimmune diseases and accelerate the development of effective drugs for a range of conditions. The support of leading deep tech and biotech investors will catalyse this unique convergence of biology and engineering.

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Bit Bios enter button for the keyboard to the software of life nabs the company $41.5 million - TechCrunch

Cell Biology

Creating the first 3D neural map of a heart – News-Medical.net

What led you to begin this research?

We have been working in the domain of the visceral emotional neuraxis for some time. This visceral emotional neuraxis is where there is an interplay between the state of peripheral organs, mood and mental function, and so on.

It is well known that stress has a detrimental effect, particularly at the heart and probably at other organs. There is a whole system of communication between the brain and the organs that subserves this and allows this interplay between visceral state and emotional state.

The health of the peripheral organs depends on that interplay operating properly. When it does not, you get, for example, heart failure and heart disease. At the same time, it has been demonstrated under some conditions that you can improve a diseased organ by improving the way that the innervation of the organ is operating by getting it into a more healthy domain.

These are all interesting scientific and clinical questions, but it is a topic that has not gotten a huge amount of support and funding. It tends to, as they say, fall between two stools. It is not quite neurology, and it is not quite cardiology. It is there and it is known about, but it is not really focused on.

A program came along called SPARC. It is not focused on neurology or the heart, or lungs, blood or any specific traditional area. It is an overarching scheme that tries to address opportunities that are not being chased by specialist organizations.

A large program was put together with the goal of providing a comprehensive mapping of the relationship between autonomic outflow and, particularly, the vagus nerve and peripheral organs, including the heart, which we are interested in.

The initial phases of it were foundational. The goal was, "Let's see what this is all about. How is this thing organized? How does it work?", and to use those answers as a springboard for getting into more clinical studies. We applied and eventually were able to receive some support, and this work is the byproduct of the contribution to that effort.

It has been a fairly longstanding interest to get to the function beyond the structure. This first attempt looked at the anatomical and molecular structure of the system. Ultimately, the goal is to figure out the function of the system.

Heart disease is very common and by far the biggest cause of death worldwide. People suffer mightily from heart disease. They may have a considerable amount of pain for some time or be very reduced in their functionalities.

The pharmaceutical approaches that have been taken so far have been somewhat efficacious. They are not worthless, but they are far from addressing the problem.

The development of devices to manipulate the activity of the peripheral nerves would potentially be a great positive influence in understanding and dealing with organ health - in this case, heart health.

It is really important to unpack the neural computation and circuit part surrounding organs in order to be able to better view, design, and test these devices and make them safe. So far, we do not know enough to be able to make those devices effective and safe.

The key to this is to develop a detailed anatomical molecular and functional map of the system of the heart itself. For example with the vagus nerve, you could essentially stop the heart completely if you altered this in the wrong way.

In one route, the central nervous sends an axon out to its target and innervates the muscle or the skin directly. That trafficking and communication is direct and back and forth between the peripheral target and the central nervous system.

However, what often surprises people is that there is a parallel nervous system called the autonomic nervous system in which that is not the case. In the autonomic nervous system, there are neurons interposed between the nerves coming out from the brain and the end organ.

So in our case of the heart, that means that there is a whole nervous system that is intermediate, like a little brain in the heart. It is the effector that is affecting the heart, not the brain.

This is something that is not actually that widely known, even within cardiologists. The neurons tend to be embedded in fat pads on the atria and in the ventricles in humans.

All the positive effects that the outflow from the brain has on the end-organ must pass through these intermediate neurons embedded in the heart.

People have been studying these neurons, but there has been far less than a comprehensive appreciation of their number, organization, distribution, and certainly not their molecular identities and phenotypes. We are beginning to fill in these gaps.

Raj carried out research that showed that there is a tremendous amount of local activity within this system, that does not depend on the brain. The heart does communicate sensory stuff information with the brain, but on a moment to moment basis, it has a closed-loop system taking care of things locally.

We looked for control properties and showed that there is much potential for local computation in a way that simplifies the problem for the brain to regulate. We were not dealing with a comprehensive map like we are today.

Now that we have this complexity, we want to see if we can turn that into a dynamic understanding of how all these molecules lead to certain controlling properties. What kind of local computation happens? There are some fascinating questions to chase, now that we have this comprehensive foundational substrate.

In the next phase, one of the things that we are doing is working with Peter Hunter in Auckland, New Zealand, who is developing an abstraction of the heart which he called a scaffold.

We are mounting our mapping into that scaffold in such a way that there is now an independent objective 3D representation of the heart and of the heart's nervous system, in such a way that other data can be integrated into it.

Image Credit: Intrinsic and extrinsic innervation of the heart in zebrafish ( D anio rerio ): Zebrafish Cardiac Innervation - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Organization-of-intracardiac-nervous-system-demonstrated-with-acetylated-tubulin-AcT_fig1_272844021

A small company in South San Francisco called 3Scan developed this KESM technology.

We had just taken a rat heart and taken something called the cryostat, a device that takes a larger piece of tissue like a heart and turns it into tissue sections that can be mounted onto glass slides for looking at under the microscope. In doing this we were a little bit limited by the fact that the heart has got these giant chambers that can collapse in different ways.

What we wanted to achieve was to take the data that is present at each slide, as stained neurons, and stack those sections along with the mapping of the neurons back into a 3D representation of the whole organ with the correct positioning of those neurons. But when each one of those sections is distorted to a fair extent, the outcome is not accurate.

One of the things that cause this problem is called the banana problem. If you have a banana and it has got a curve, and you cut it into thin slices and then put the slices back together by stacking them you are going to lose the curve they are just going to be straight up and down. It is not going to look like a banana.

What knife-edge does is take a diamond knife that is transparent meaning that the microscope can see the tissue through it. The diamond knife is sectioning at five microns, which is pretty thin. A microscope camera system is then capturing digital images of the section as it is being sectioned, at a resolution of about a half a micron by a half a micron pixel size.

Due to the very high-resolution image of the tissue section in situ, you are capturing a detailed image of the section itself which means that the stack is going to be exactly the same as the original organ with no distortions. That is knife-edge scanning microscopy.

The second part of the problem is that there is a lot of data. If you are doing it manually with whole slice imaging, depending on how the slide is imaged even the stacking may not be that straightforward to do and the alignment becomes a problem even after you have a reference frame to get around the banana problem.

What the KESM system was doing was not only acquiring images within one reference frame but setting the whole system up for high data throughput. The mass of data that you collect and sort is integrated into the whole KESM system in such a way to make a downstream analysis much easier. That makes a world of a difference.

KESM was the first part of it, acquiring the rat hearts and getting the image data. That was quite a large volume of image data.

We have a second collaborator called MicroBrightField, MBF Biosciences. Their specialty is software for 3D mapping of tissue sections from the brain and subsequent 3D reconstructions of regions of the brain.

However, they modified their software to work with the heart. Using their TissueMaker and Tissue Mapper software, they were able to take data from 3Scan and turn it into a stack of images mappable by the software.

We have other collaborators in Orlando, Florida at UCF, as well as ours in Philadelphia, who had used that software to create these mappings and these 3D representations.

It has very much been a joint effort. A lot of teamwork has been involved, for which I am proud of. The key was that everybody was sold on what the goal and purpose of this is. To get to that 3D map at a very high resolution was a unique once in a lifetime opportunity. An essential element was to let the data speak for itself and not bias it with what we thought the biology ought to be.

The rat heart is the most widely used model of physiology, pharmacology, and biochemistry. It has similarities to humans but is also widely different.

It is important to have a clear picture of the organization of neurons in the rat. The prior literature tends to focus on what is called the base of the heart. It seems counterintuitive, but the base of the heart is the top of the heart. This comes from embryology as the heart grows from the top down, and so the base is the origin of the heart, where it grows from. Then it grows down to the so-called apex at the bottom of the ventricles.

The base of the heart (hilum) is where the focus of this neural system has been. The hilum of any organ is the region in which the vessels that serve it enter and exit. So you have arteries and veins the pulmonary artery, the aorta, pulmonary veins, and so on going in and out of this region.

In development, the neurons migrate into the heart, down the vessels, and then just scatter out. The thought was that you are going to wind up with this very variable, disorganized, and haphazardous scattering of neurons.

This is not what we actually saw when we were able to put the thing back together. There is quite a lot of innervation coming from the hilum around the vessels, especially with the pulmonary veins and around the vena cava.

These clusters are almost like a continuous sheet of neurons that extend out of the hilum. One of the places they go to is the thin membrane separating the atria called the interatrial septum.

The clusters continue down the left atrium on the posterior surface of the heart, and those clusters are substantial. They are not continuous - they are distinct clusters that extend all the way to the ventricular boundary. That was a big surprise.

The next thing that we have done looked across quite a few different hearts. What we found is that they are actually quite consistent with one another and it is not a random or wildly variable situation at all.

Having a full map starts opening up new possibilities to say: Are these clusters the same? How are they different? In what ways can they be exhibiting distinct functions, or are they there for redundancy? Suddenly the way we ask those questions might change because the path at least has been refined in a very substantive way.

One of the important questions before going into this was what is the level of complexity of these neurons? Are they mostly based on one or two types of molecules that they use to communicate? Are they cholinergic? Do they use adrenaline or adrenergic neurons? Most of the literature that has been out there describe it as a two-part system.

For a long time, these things were thought of as a nuance that could not do much, because the brain must be where everything happens.

Here, we went into single neuron gene expression, and that in itself was a technically challenging feat. Laser capture microdissection was needed and most importantly spatially tracking where we were getting these neurons from so that they could be put back together into the map.

When looking at that gene expression that is spatially tracked, there is a tremendous amount of complexity. There is a wide range of neurotransmitters in the neuromodulatory system present. And so, the potential for computation is immense. On top of it, there were not distinct types of neurons that they broke down into distinct neuropeptides. There were not distinct sets of neurons that made distinct neuromodulators. We see a combinatorial logic at play.

The way we have to think about the problem is not that there are completely distinct parts that somehow come together, but rather every neuron has some capability to do many, many things. Multiple neurotransmitters and neuromodulator processes can be activated and flexibly used in each neuron.

And so, how would that system operate? It opens up a lot of new questions into how we think about plasticity and adaption within this process. There is a story that connects this to the brain and molecular gradients.

We are following behind the technologies that have been recently developed in the brain. The leader there was the Allen Institute.

They have developed technologies together with MicroBrightField (MBF) and have been the leader in figuring out how to make these kinds of molecular atlases. What they have found consistently is that the neurochemical properties or the molecular phenotypes are present in gradients throughout the different parts of the cerebral cortex. You see modulators and transmitters and receptors distributed in gradients.

That is what we were looking for at the heart as well. And indeed, there are gradients. It is not like all the neurons do the same thing. The distribution of cardiac neurons are differentially expressing modulators and transmitters and receptors.

They do so in an interesting way that suggests that in addition to direct neuron-to-neuron function, there could also be opportunities for paracrine function, that is, a cluster of neurons might be bathed in a modulator so as to alter the population activity. This provided opportunities to start thinking about interventions much more broadly.

It was weakly known that there was more at the heart than acetylcholine and norepinephrine, but fundamentally that is how people have thought about the system that the neurotransmitter that is used by the neurons at the heart is acetylcholine and there is a modulation from norepinephrine inputs, but that is about it.

Through our research, the heart neuronal system has been shown to be more interesting, more complex, and more organized than previously thought. There looks to be a fundamental structural organization to the heart's nervous system both in terms of its clustering, its distribution, and the kinds of modulatory factors and receptors that it employs.

MBF Biosciences was our exclusive collaborator and subcontractor on our grant for doing the heart. However, once the SPARC leadership saw what we were getting, they snatched them off into what they call MAPcore, where they are working with all the other organs in the SPARC program, such as the pancreas, the bladder, and the intestine.

Also, there were so many lessons learned in working with the heart, not just in KESM and with MBF Biosciences, but with how to annotate and share that information and turn it into a more generalizable scaffold.

The vision for SPARC is to have all this data in a single, highly structured, annotated, and accessible resource that is available to the community in every way. The hope is that this will be a heavily used resource that will get populated with additional relevant data sets that have used it.

The only thing that stands between us and that is money.

There are a few technology scaleups that have to be made, but none of them are insurmountable. It is very clear what it is that we have to do, and we have given it much thought. A lot of detailed planning has occurred on how one might go about that.

We have even scaled some of this to a small chunk of a pig heart. The pig heart is huge - it is as big as a human heart and it is more similarly organized to a human heart. It is not exactly the same, but it is a good scaleup.

We think the human heart will be done in less than a decade, given that so many things have been figured out in the pipeline and the key is timing. As with anything, when people gather around, put their collective brains and technologies together to work on a problem and it is all fresh in the mind, that is the time to do it.

Image Credit: Africa Studio/Shutterstock.com

One is the therapeutic or protective effects of the vagal activity on the heart passing through these neurons. If you could associate the protective or therapeutic activity to specific neurons and modulators, you could emulate that either by finding the right stimulation parameters or feeding with the right molecular manipulations.

Another step that would really help augment our efforts to develop interventions is getting a sense of dynamics of the system. We need to develop into how these parts move about and interact with each to yield certain network dynamics.

When we develop that initial understanding, that would help prioritize and narrow down the intervention possibilities instead of just relying on static anatomical snapshot data. This is a substrate on which dynamic simulations and models will be built.

We have explored the variability across hearts in both males and females, a paper that is just about done. In another direction, we have begun to explore mounting these data sets into Peter Hunter's Auckland Bioengineering Institute scaffold.

We have also started to build dynamic models of the system to examine what control properties they exhibit, and how they would play in circuits together with the central nervous system. That is the grant we do not have funding for but hope will be funded July 1st.

I think this SPARC effort out of the common fund in the Director's Office has been successful and is doing what it intended to do, which is to begin to make not a third stool between the two, but a bridge.

Hopefully, we are heading in a direction where the individual institutes will then invest in making people cross those bridges and connect two disparate fields towards improving human health in ways that have not been possible before this.

Read the iScience paper here: https://doi.org/10.1016/j.isci.2020.101140

SPARC portal: https://sparc.science/

Rajanikanth Vadigepalli, Ph.D., is Vice-Chair of Research and Professor of Pathology, Anatomy, and Cell Biology at Thomas Jefferson University.

Dr. Vadigepallis collaborative research program at the Daniel Baugh Institute for Functional Genomics/Computational Biology is driven by a convergence of systems engineering, computational modeling, bioinformatics, and single-cell scale transcriptomics, to identify and target key control points for intervention in disease.

Ongoing international collaborative projects focus on central and peripheral neural circuits controlling the heart, brainstem neuroimmune processes leading to hypertension, liver regeneration in alcoholic liver disease, and cell fate regulation underlying developmental defects.

James Schwaber, Ph.D., is Director of the Daniel Baugh Institute for Functional Genomics and Computational Biology and Professor of Pathology, Anatomy & Cell Biology.

Dr. Schwaber uses systems biology approaches in the mammalian brain to study adaptive neuronal processes.

His main interest is in the emotionalvisceral neuraxis and disorders involving this interaction, including those related to stress and autonomic imbalance in neurogenic contributions to hypertension, addiction and withdrawal from the dependent state, and neurodegenerative conditions including epilepsy.

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Creating the first 3D neural map of a heart - News-Medical.net

Cell Biology

Close to 2,000 Faculty, Staff Return to Work as Some Harvard Labs Resume Research Operations | News – Harvard Crimson

Nearly 2,000 faculty and staff members returned to scientific research laboratories at Harvard over the past week the first large scale return to work since campus shut down in mid-March due to the coronavirus pandemic.

University Provost Alan M. Garber 76 announced on May 4 that Harvard would begin a phased reopening of Harvards research labs, which he described as urgent.

The return to research operations is overseen by a Lab Reopening Committee, initially formed by Vice Provost for Research Richard D. McCullough in collaboration with Dean of Science Christopher J. Stubbs at Garber's request.

The labs operate in shifts and use physical distancing and personal protective protocols. They are modeled after guidelines used by University labs dedicated to COVID-19 research, which have remained open as essential work.

Naina Kurup, a postdoctoral fellow in the Chemistry Department, wrote in an email that the guidelines have contributed to a sense of security, though there has been a learning curve for certain requirements, like avoiding common spaces and completing online check-ins.

Nevertheless, Kurup wrote that she and others in the lab are slowly finding our groove again."

It's been exciting to see my worms come back to life again so I can start the experiments I was planning at home! she wrote.

Though researchers are social distancing, Professor of Engineering and Applied Sciences Conor J. Walsh said his labs ability to return to in-person experiments is positive, noting its work is experimental in nature and cannot be done at home.

For us, we're not able to do the types of research we are without being in the lab, he said.

Stem Cell and Regenerative Biology Professor Richard T. Lee 79, a former Crimson editor, said the reopening of his lab is crucial because its work relies on experiments.

We could write up some papers and write proposals, but we weren't getting new data, he said. We were very much shut down by the shutdown.

Still short of full capacity, Lee said researchers must be much more strategic about time spent in the lab.

We're trying to get those answers now as quickly as we can, he said. We're not at full capacity and so we have to be very careful about every person, hour in the lab.

Though Lee is overseeing the lab, he said that he himself has not returned to the lab, since his presence would take up one of the density spots the number of researchers authorized to work in the lab at a given time and.

Mohammed Mostafizur Rahman, a postdoctoral fellow in the Department of Molecular and Cellular Biology, said that he spent much of last week in preparation for future experiments.

For all the work that we shut down, we need time to ramp up as well, he said. This first week hasn't been really much work as much as prep for the work a lot of animal breeding, getting animals ready, getting your reagents ready.

Leonardo A. Sepulveda Duran, a postdoctoral fellow in the Chemistry Department, said that he, too, is seeking to be strategic about his work in case the pandemic closes labs again.

I'm focusing on just trying to get the most data I can in a few next months, so if we have to go into lockdown again, I can do the analysis of the data remotely, the same way I've been doing, Sepulveda Duran said. I imagine this is going to happen several times until we get a vaccine.

For now, though, most said they are happy to be back to work.

As an experimentalist, there's no other place you want to be than in your lab, Rahman said.

Staff writer Camille G. Caldera can be reached at camille.caldera@thecrimson.com. Follow her on Twitter @camille_caldera.

Staff writer Michelle G. Kurilla can be reached at michelle.kurilla@thecrimson.com. Follow her on Twitter @MichelleKurilla.

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Close to 2,000 Faculty, Staff Return to Work as Some Harvard Labs Resume Research Operations | News - Harvard Crimson

Cell Biology

Sales Forecasts of Tooth Regenerations Market Reveal Positive Outlook Through 2026 – 3rd Watch News

The tooth is a biological organ and consists of multiple tissues including the cementum, dentin, enamel, and pulp. Dental caries, Periodontal disease, and tooth fracture are the three main factor for tooth loss. Tooth Regeneration is the specialty concerned with the treatment of dental diseases such as a cavity, periodontal disease and fracture of the tooth. Dental caries is also known as tooth decay is the main oral health problems in most of the industrialized countries. Facial trauma also the major cause of tooth loss. Tooth loss leads to people mentally and physically disturb and it also affect the self-confidence and quality of life. Tooth regeneration is the process of individual tissue and the whole tooth development. Basically, it is the process of restoring the loss of natural teeth. Tooth regeneration is stem cell-based regenerative medical procedure which is used in stem cell biology sector and tissue engineering. There are two approaches used in the build of new whole teeth, in vivo implantation of tooth germ cells which were previously generated from stem cells and grow in vitro cells and another organotypic culture is an appropriate technique for the generation of teeth.

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Globally increasing incidence and prevalence of dental problems such as a cavity, periodontal disease, and tooth fracture are the major factors driving the growth of the Tooth Regenerations market. Innovative new techniques in Tooth regeneration such as cell homing, cell transplantation is expected to increase the acceptance of Tooth Regenerations. Tooth regeneration not only regrowth the entire tooth but also the restoration of individual components of the tooth such as dentin, cementum, enamel and dental pulp and these individual regeneration process is anticipate the boost the market growth of tooth regeneration market. Dental implantation also increases the growth of tooth regeneration market. People are very keen interested in the tooth regeneration and they are also giving more importance to the aesthetic aspects of dental products, which is expected to increase the Tooth Regenerations and dental market over the forecast period. The increasing demand for a customized Tooth Regeneration with the specifications and other dental decorative installations is the key factor anticipated to propel the demand for Tooth Regenerations worldwide.

The Global Tooth Regenerations market is segmented on the basis of application, Demographics, technique and by End user

Based on the Application type Tooth Regenerations market is segmented as:

Based on the Demographic Tooth Regenerations market is segmented as:

Based on the Technique, Tooth Regenerations market is segmented as:

Based on the end user Tooth Regenerations market is segmented as:

According to WHO, approx.30% the geriatric population is affected by the complete loss of teeth. Rapidly increasing Dental cavities and periodontal diseases are the major drivers in the Tooth Regenerations market. The global Tooth Regenerations market by application is expected to be dominated the market of Tooth Regenerations, out of which Enamel segment is expected to generate maximum revenue share over the forecast period. By end user, Tooth Regenerations market is expected to be dominated by dental clinics and hospitals. The manufacturers in the concerned market are focusing on manufacturing advanced products for better patient compliance and make the procedure easier. The market of tooth regeneration is anticipated to boost by stem cell regeneration technology

The global Tooth Regenerations market is expected to be dominated by North America due to higher adoption and significant geriatrics population which also increase the demand for dental service for Dental caries and Periodontal disease. Europe is expected to be the second most lucrative Tooth Regenerations market due to rising funds for research for the growing patient population. Asia-Pacific is expected to be the fastest growing Tooth Regenerations market due to rapidly increasing incidence of dental surgery, general prosthetic fixation. Latin America and Middle East & Africa are expected to be the least lucrative market due to Low awareness regarding the use of Tooth Regenerations technology and comparatively less developed healthcare infrastructure in major regions.

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Examples of some of the market participants in the global Tooth Regenerations market identified are DENTSPLY Implant, Unilever, Datum Dental, Institut Straumann AG, Keystone Dental, Inc., Zimmer Biomet, Wright Medical Group N.V., Integra LifeSciences, CryoLife, Inc, BioMimetic Therapeutics, Inc, Cook Group and among others.

The report is a compilation of first-hand information, qualitative and quantitative assessment by industry analysts, inputs from industry experts and industry participants across the value chain. The report provides in-depth analysis of parent market trends, macro-economic indicators and governing factors along with market attractiveness as per segments. The report also maps the qualitative impact of various market factors on market segments and geographies.

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Sales Forecasts of Tooth Regenerations Market Reveal Positive Outlook Through 2026 - 3rd Watch News

Cell Biology

GLOBAL HUMAN EMBRYONIC STEM CELL MARKET Analysis 2020 With COVID 19 Impact Analysis| Leading Players, Industry Updates, Future Growth, Business…

With a full devotion and dedication this superior GLOBAL HUMAN EMBRYONIC STEM CELL MARKET report is presented to the clients that extend their reach to success. Market parameters covered in this advertising report can be listed as market definition, currency and pricing, market segmentation, market overview, premium insights, key insights and company profile of the key market players. Each parameter included in this GLOBAL HUMAN EMBRYONIC STEM CELL MARKET business research report is again explored deeply for the better and actionable market insights. Geographical scope of the products is also carried out comprehensively for the major global areas which helps define strategies for the product distribution in those areas.

TheGlobal Human Embryonic Stem Cell Marketstudy with 100+ market data Tables, Pie Chat, Graphs & Figures is now released by Data Bridge Market Research. The report presents a complete assessment of the Market covering future trend, current growth factors, attentive opinions, facts, and industry validated market data forecast till 2026. Delivering the key insights pertaining to this industry, the report provides an in-depth analysis of the latest trends, present and future business scenario, market size and share ofMajor Players such as Arizona Board of Regents, STEMCELL Technologies Inc, Cellular Engineering Technologies, CellGenix GmbH, PromoCell GmbH, Lonza, Kite Pharma, Takeda Pharmaceutical Company Limited, BrainStorm Cell Limited., CELGENE CORPORATION, Osiris Therapeutics,Inc, U.S. Stem Cell, Inc and amny More

Global human embryonic stem cell market estimated to register a healthy CAGR of 10.5% in the forecast period of 2019 to 2026. The imminent market report contains data for historic year 2017, the base year of calculation is 2018 and the forecast period is 2019 to 2026. The growth of the market can be attributed to the increase in tissue engineering process.

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Market Dynamics:

Set of qualitative information that includes PESTEL Analysis, PORTER Five Forces Model, Value Chain Analysis and Macro Economic factors, Regulatory Framework along with Industry Background and Overview.

Global Human Embryonic Stem Cell Market By Type (Totipotent Stem Cells, Pluripotent Stem Cells, Unipotent Stem Cells), Application (Regenerative Medicine, Stem Cell Biology Research, Tissue Engineering, Toxicology Testing), End User (Research, Clinical Trials, Others), Geography (North America, Europe, Asia-Pacific, South America, Middle East and Africa) Industry Trends and Forecast to 2026

Global Human Embryonic Stem Cell Research Methodology

Data Bridge Market Research presents a detailed picture of the market by way of study, synthesis, and summation of data from multiple sources.The data thus presented is comprehensive, reliable, and the result of extensive research, both primary and secondary. The analysts have presented the various facets of the market with a particular focus on identifying the key industry influencers.

Major Drivers and Restraints of the Human Embryonic Stem Cell Industry

Complete report is available (TOC) @https://www.databridgemarketresearch.com/toc/?dbmr=global-human-embryonic-stem-cell-market

The titled segments and sub-section of the market are illuminated below:

By Type

By Application

By End User

Top Players in the Market are:

Some of the major companies functioning in global human embryonic stem cell market are Arizona Board of Regents, STEMCELL Technologies Inc, Cellular Engineering Technologies, CellGenix GmbH, PromoCell GmbH, Lonza, Kite Pharma, Takeda Pharmaceutical Company Limited, BrainStorm Cell Limited., CELGENE CORPORATION, Osiris Therapeutics,Inc, U.S. Stem Cell, Inc, Waisman Biomanufacturing, Caladrius, Pfizer Inc., Thermo Fisher Scientific, Merck KGaA, Novo Nordisk A/S, Johnson & Johnson Services, Inc and SA Biosciences Corporation among others.

How will the report help new companies to plan their investments in the Human Embryonic Stem Cell market?

The Human Embryonic Stem Cell market research report classifies the competitive spectrum of this industry in elaborate detail. The study claims that the competitive reach spans the companies of.

The report also mentions about the details such as the overall remuneration, product sales figures, pricing trends, gross margins, etc.

Information about the sales & distribution area alongside the details of the company, such as company overview, buyer portfolio, product specifications, etc., are provided in the study.

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Some of the Major Highlights of TOC covers:

Chapter 1: Methodology & Scope

Definition and forecast parameters

Methodology and forecast parameters

Data Sources

Chapter 2: Executive Summary

Business trends

Regional trends

Product trends

End-use trends

Chapter 3: Human Embryonic Stem Cell Industry Insights

Industry segmentation

Industry landscape

Vendor matrix

Technological and innovation landscape

Chapter 4: Human Embryonic Stem Cell Market, By Region

Chapter 5: Company Profile

Business Overview

Financial Data

Product Landscape

Strategic Outlook

SWOT Analysis

Thanks for reading this article, you can also get individual chapter wise section or region wise report version like North America, Europe or Asia.

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GLOBAL HUMAN EMBRYONIC STEM CELL MARKET Analysis 2020 With COVID 19 Impact Analysis| Leading Players, Industry Updates, Future Growth, Business...

Cell Biology

Enduring research: The constant threat of influenza virus outbreaks – Open Access Government

In light of the on-going global SARS-CoV-2 outbreak, that is keeping world health hostage, severely paralysing the world economy and strongly restricting social life, we are now experiencing the impact of a pandemic and how much the life as we know it depends on the options we have to stand up against such threats. This becomes even more relevant when one considers that this virus is just one of a multitude of viral foes with highly devastating potential.

The SARS-CoV-2 belongs to the large group of viruses that possess an RNA genome and has made its way from the animal kingdom into humans causing a zoonosis, which has spread around the world. The vast majority of newly emerging and re-emerging infectious diseases are caused by RNA viruses, with West Nile-, Ebola-, influenza-, and SARS viruses being prominent examples. RNA viruses have an enormous genetic plasticity, facilitating rapid adaptation of animal RNA viruses to new hosts including humans and rapid development of resistance against (directly acting) antiviral drugs. Such zoonotic RNA viruses may cause major outbreaks and severe disease in humans, especially in cases where there is no pre-existing immunity in the human population, exemplified by the current pandemic.

As such, the influenza A viruses (IAVs) stand out among these potential enemies. Their natural reservoir are aquatic birds and IAVs possess a great zoonotic potential as they can infect different avian and mammalian animal hosts, from which they can be transmitted to humans. This is based on their ability to gradually change their genome by mutation or even reassemble their genome segments during co-infection of the host cell with different IAV strains, resulting in a high genetic diversity1.

The devastating Spanish Flu led to the most dramatic pandemic of the last century, globally killing more than 25 million people within 25 weeks between 1918/1919. Subsequently, a new pandemic strain the Asian Flu emerged in 1957 leading to at least one million fatalities. In 1968, the pandemic Hong Kong Flu emerged, resulting in about one million deaths. In 1977, Russian Flu spread worldwide, causing severe infections in humans with a 50% fatality rate among school-aged children. In 2009, a reassortant IAV with a unique genome constellation most likely generated in pigs led to the first pandemic of the current century, known as Swine Flu [1 and references therein].

Among the available options for control and prevention of IAV infections, vaccination is still the primary option and the most effective method to combat IAV infection. As seen with the efforts undertaken to develop a vaccine against SARS-CoV-2 this takes time and a potential vaccine will not be available at the start of an outbreak caused by a yet unknown virus. To establish the first line of defence against newly emerging IAV, for which vaccines are generally not available, potent and broadly acting antivirals are urgently needed. Ideally, these compounds should be widely available, have broad-spectrum activity against a range of IAV and be unlikely to cause viral resistance.

Currently, all approved and most of the antivirals in development act directly against the virus [1 and references therein]. As IAVs can quickly adapt to these directly acting selective pressures, such therapeutic approaches lose their effectiveness over time. Nevertheless, all viruses absolutely depend on services provided by the infected host cell. To address the problem of viral resistance in antiviral drug development, the work of the authors pioneered in the identification and inhibition of specific cellular (rather than viral) functions/factors that are essential for IAV. The highly specific inhibition of cellular functions is expected to fulfil most, if not all, of the above requirements, preventing efficient viral replication when the respective cellular factor is impaired. The combined and long-lasting collaboration between the three laboratories of the authors has successfully demonstrated that this approach possesses a great potential to define novel and effective antivirals by in-depth basic molecular virological research.

In 2001, we demonstrated for the first time that a specific virus-induced intracellular signalling event the Raf/MEK/ERK cascade is essential for efficient production of infectious IAV progeny. IAV replicate their genomes by their own polymerases within the nucleus of the infected cell and thus need to export their genome from nucleus to the cell membrane where virus particles form to be released. Inhibition of the cascade by specific inhibitors, which block this pathway at the level of the kinase MEK results in nuclear retention of viral genome complexes (RNPs) and concomitantly inhibits virus production2. The relevance of this cascade for IAV was then further demonstrated in vivo in mice3 and moreover also for influenza B viruses (IBV), which together with IAV cause seasonal epidemics. Importantly, neither IAV nor IBV develops resistance under treatment4.

Analysis of the functional role of the cascade within the viral replication cycle established that cell membrane accumulation of the viral HA-protein triggers activation of the cascade and induces nuclear RNP export. This represents an auto-regulative spatial-temporal coordination of nuclear RNP export to a point when all viral components are ready for virus budding5. More recent results indicate that the cascade does not affect nuclear export in general, for example, by interfering with the cellular nuclear export machinery, but rather specifically acts on the export of viral vRNPs by controlling specific modifications of viral proteins.

Interestingly, among human IAVs, those possessing a higher polymerase activity lead to more HA production and enhanced activation of the HA-induced Raf/MEK/ERK signal cascade6. Apart from tissue damage caused by the virus lytic replication, an imbalanced overproduction of antiviral cytokines can cause severe lung damage as observed in human infections with highly pathogenic avian influenza viruses (HPAIV). We showed that inhibition of the signalling cascade decreased both, virus titres and cytokine expression. This was not only true in vitro, but also in infected mice. Hereby we could demonstrate for the first time that IAV titres and pro-inflammatory cytokine expression can be modulated simultaneously7.

We continued our investigations with the experimental MEK inhibitor U0126, validating its ability to suppress propagation of the 2009 pandemic IAV (H1N1pdm09), as well as HPAIV in cell culture and also in vivo in the mouse lung. Notably, U0126 impaired all tested IAV strains, including oseltamivir (Tamiflu) resistant variants. Furthermore, treatment of mice with U0126 via the aerosol route led to the protection of IAV-infected mice against a 100x lethal viral challenge. Moreover, no adverse effects were detected in cell culture or in the mouse8.

As U0126 is an experimental substance, we aimed to elucidate the efficacy of a compound that was tested in clinical investigations aiming to translate our research into the development of a therapeutic approach. In consequence, we studied the antiviral potential of the clinically tested MEK inhibitor Cl-1040 against various IAV. CI-1040 was originally developed as an anti-tumour drug where it showed low toxicity. We found that Cl-1040 significantly reduces virus titres in vitro and is effective against a broad range of IAV strains, including HPAIV, as well as against a Tamiflu-resistant IAV strain and, that it reduces IAV lung titres in vivo a mouse model. Importantly, the treatment window for Cl-1040 expands up to 48 h post-infection when Tamiflu treatment has lost its effectiveness9.

Most recently we compared the antiviral potency of CI-1040 versus its major active metabolite ATR-002, in vitro as well as in the mouse model. In cell culture assays, approximately 10-fold more ATR-002 is needed for the same antiviral activity as CI-1040. Interestingly, considerably lower concentrations of ATR-002 were required to reduce the viral load in vivo. Pharmacokinetic studies showed a far higher bioavailability for ATR-002 than for CI-1040 demonstrating the in vivo superiority of ATR-002 as an antiviral agent, despite its weaker cell membrane permeability10.

Since the Raf/MEK/ERK pathway is activated by many RNA viruses11, it was a valid assumption that also other viruses may exploit this signalling pathway and may be sensitive to MEK inhibition. This was confirmed in studies on the replication of Borna Disease viruses12 or Respiratory Syncytial viruses13, which was efficiently blocked by MEK inhibition, albeit by mechanisms different of that found for IAV.

The enormous potential of inhibiting cellular MEK in the fight against RNA viruses becomes particularly relevant in the face of the COVID-19 crisis. Previous work by others has shown that the membrane-located S-protein of the 2003 SARS-CoV is involved in the induction of the Raf/MEK/ERK pathway. Furthermore, infection of cultured cells with mouse hepatitis virus (MHV) a murine coronavirus also activated the signal cascade, and the investigative MEK inhibitor U0126 significantly impaired MHV replication. The inhibitory effect of U0126 on MHV appeared to be a general phenomenon observed in all six different MHV strains and in three different cell types tested [11 and references within]. This tempts us to speculate that MEK inhibitors, such as ATR-002, could possibly be effective against SARS-CoV-2.

Meanwhile, our work is being actively translated into a therapeutic approach in collaboration with Atriva Therapeutics, Germany, and ATR-002 has by now undergone pharmacokinetic studies, as well as a very successful Phase I clinical study. This randomised, double-blind, placebo-controlled dose escalation study demonstrated the safety and tolerability of ATR-002 and the observed pharmacokinetic profile supports the intended once-daily regime for the further Phase II clinical development. Potential advantages of this host-targeting approach are the prolonged treatment window and the reduced potential of viral resistance, both compared to therapies that directly target viral structures.

Our brief summary recapitulating 19 years of collaborative work in basic virological research clearly shows that continuing funding of such efforts has a great potential to provide a health benefit to European societies.

Stephan Pleschka1*, Oliver Planz 2, Stephan Ludwig 3

1 Institute for Medical Virology, Justus Liebig University, Giessen, GermanyGerman Center for Infectious Research (DZIF), Partner site Giessen, Germany.

2 Institute of Cell Biology and Immunology, Eberhard Karls University Tuebingen, Germany.

3 Institute of Virology, Westfaelische-Wilhelms-University Muenster, Germany.

References

1 Mostafa A, Abdelwhab EM, Mettenleiter TC, Pleschka S. 2018. Zoonotic Potential of Influenza A Viruses: A Comprehensive Overview. Viruses 10.

2 Pleschka S, Wolff T, Ehrhardt C, Hobom G, Planz O, Rapp UR, Ludwig S. 2001. Influenza virus propagation is impaired by

inhibition of the Raf/MEK/ERK signalling cascade. Nat Cell Biol 3:301-305.

3 Olschlager V, Pleschka S, Fischer T, Rziha HJ, Wurzer W, Stitz L, Rapp UR, Ludwig S, Planz O. 2004. Lung-specific expression of active Raf kinase results in increased mortality of influenza A virus-infected mice. Oncogene 23:6639-6646.

4 Ludwig S, Wolff T, Ehrhardt C, Wurzer WJ, Reinhardt J, Planz O, Pleschka S. 2004. MEK inhibition impairs influenza B virus propagation without emergence of resistant variants. FEBS Lett 561:37-43.

5 Marjuki H, Alam MI, Ehrhardt C, Wagner R, Planz O, Klenk HD, Ludwig S, Pleschka S. 2006. Membrane accumulation of

influenza A virus hemagglutinin triggers nuclear export of the viral genome via protein kinase Calpha-mediated activation of ERK signaling. J Biol Chem 281:16707-16715.

6 Marjuki H, Yen HL, Franks J, Webster RG, Pleschka S, Hoffmann E. 2007. Higher polymerase activity of a human influenza virus enhances activation of the hemagglutinin-induced Raf/MEK/ERK signal cascade. Virol J 4:134.

7 Pinto R, Herold S, Cakarova L, Hoegner K, Lohmeyer J, Planz O, Pleschka S. 2011. Inhibition of influenza virus-induced NF-kappaB and Raf/MEK/ERK activation can reduce both virus titers and cytokine expression simultaneously in vitro and in vivo. Antiviral Res 92:45-56.

8 Droebner K, Pleschka S, Ludwig S, Planz O. 2011. Antiviral activity of the MEK-inhibitor U0126 against pandemic H1N1v and highly pathogenic avian influenza virus in vitro and in vivo. Antiviral Res 92:195-203.

9 Haasbach E, Muller C, Ehrhardt C, Schreiber A, Pleschka S, Ludwig S, Planz O. 2017. The MEK-inhibitor CI-1040 displays a broad anti-influenza virus activity in vitro and provides a prolonged treatment window compared to standard of care in vivo. Antiviral Res 142:178-184.

10 Laure M, Hamza H, Koch-Heier J, Quernheim M, Muller C, Schreiber A, Muller G, Pleschka S, Ludwig S, Planz O. 2020.

Antiviral efficacy against influenza virus and pharmacokinetic analysis of a novel MEK-inhibitor, ATR-002, in cell culture and in the mouse model. Antiviral Res 178:104806.

11 Pleschka S. 2008. RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade. Biol Chem 389:1273-1282.

12 Planz O, Pleschka S, Oesterle K, Berberich-Siebelt F, Ehrhardt C, Stitz L, Ludwig S. 2003. Borna disease virus nucleoprotein

interacts with the CDC2-cyclin B1 complex. J Virol 77:11186-11192.

13 Preugschas HF, Hrincius ER, Mewis C, Tran GVQ, Ludwig S, Ehrhardt C. 2019. Late activation of the Raf/MEK/ERK pathway is required for translocation of the respiratory syncytial virus F protein to the plasma membrane and efficient viral replication. Cell Microbiol 21:e12955.

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Enduring research: The constant threat of influenza virus outbreaks - Open Access Government

Cell Biology

Magenta Therapeutics and Beam Therapeutics Announce Collaboration to Evaluate Targeted Antibody-Drug Conjugate (ADC) MGTA-117 as Conditioning Regimen…

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (Nasdaq: MGTA) and Beam Therapeutics (Nasdaq: BEAM) today announced a non-exclusive research and clinical collaboration agreement to evaluate the potential utility of MGTA-117, Magentas novel targeted ADC for conditioning of patients with sickle cell disease and beta-thalassemia receiving Beams base editing therapies. Beam is pursuing two differentiated base editing approaches to treat hemoglobinopathies: its hereditary persistence of fetal hemoglobin (HPFH) program to precisely and robustly elevate fetal hemoglobin, which could be used in treatments for both sickle cell disease and beta-thalassemia, as well as a novel approach to directly correct the sickle causing point mutation (Makassar).

Conditioning is a critical component necessary to prepare a patients body to receive the edited cells, which carry the corrected gene and must engraft in the patients bone marrow in order to be effective. Todays conditioning regimens rely on nonspecific chemotherapy or radiation, which are associated with significant toxicities. MGTA-117 precisely targets only hematopoietic stem and progenitor cells, sparing immune cells, and has shown high selectivity, potent efficacy, wide safety margins and broad tolerability in non-human primate models. MGTA-117 may be capable of clearing space in bone marrow to support long-term engraftment and rapid recovery in patients.

Beam has demonstrated the ability to edit individual DNA bases in hematopoietic stem cells at high efficiency and with little impact on the viability of edited cells relative to unedited cells using its novel base editing technology. Combining MGTA-117 with Beams HPFH and Makassar base editors could meaningfully advance the treatment of patients with sickle cell disease or beta-thalassemia.

We believe patients will benefit from a more precise process to remove hematopoietic stem cells and prepare them to receive genetic medicines. Magenta has developed targeted ADCs as the preferred modality for our conditioning programs, and we have designed MGTA-117 specifically to optimize it for use with a genetically-modified cell product delivered in a transplant setting, said Jason Gardner, D.Phil., president and chief executive officer, Magenta Therapeutics. Beams next-generation base editing technology complements our next-generation conditioning approach very well, and we are excited to combine these strengths to address the still-significant unmet medical needs of the sickle cell and beta-thalassemia patient communities.

Base editing has the potential to offer lifelong treatment for patients with many diseases, including sickle cell disease and beta-thalassemia. Our novel base editors create precise single base changes in genes without cutting the DNA, enabling durable correction of hematopoietic stem cells with minimal effects on cell viability or genomic integrity, said John Evans, chief executive officer of Beam. Combining the precision of our base editing technology with the more targeted conditioning regimen enabled by MGTA-117 could further improve therapeutic outcomes for patients suffering from these severe diseases. We look forward to partnering with the Magenta team to explore these novel technologies together.

Beam will be responsible for clinical trial costs related to development of Beams base editors when combined with MGTA-117, while Magenta will continue to be responsible for all other development costs of MGTA-117. Magenta will also continue to develop MGTA-117 in other diseases, including blood cancers and genetic diseases. Each company will retain all commercial rights to their respective technologies.

About MGTA-117

MGTA-117, Magentas most advanced conditioning program, is a CD117-targeted antibody engineered for the transplant setting and conjugated to amanitin, a toxin in-licensed from Heidelberg Pharma. It is designed to precisely deplete only hematopoietic stem and progenitor cells and has shown high selectivity, potent efficacy, wide safety margins and broad tolerability in non-human primate models, suggesting that it may be capable of clearing space in bone marrow to support long-term engraftment and rapid recovery in patients. Magenta plans to complete IND-enabling studies this year and initiate clinical studies in 2021. Magenta will continue to develop MGTA-117 in other diseases, including blood cancers and genetic diseases.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients. Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com. Follow Magenta on Twitter: @magentatx.

About Base Editing and Beam TherapeuticsBeam Therapeutics (Nasdaq: BEAM) is a biotechnology company developing precision genetic medicines through the use of base editing. Beams proprietary base editors create precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This enables a wide range of potential therapeutic editing strategies that Beam is using to advance a diversified portfolio of base editing programs. Beam is a values-driven organization focused on its people, cutting-edge science, and a vision of providing life-long cures to patients suffering from serious diseases. For more information, visit http://www.Beamtx.com.

Magenta Therapeutics Forward-Looking StatementsThis press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including, without limitation, statements regarding the research and clinical collaboration agreement between Magenta and Beam, including the timing, progress and success of the collaboration contemplated under the agreement, the successful evaluation of MGTA-117 in conjunction with Beams base-editing therapies under the agreement, the anticipated cost allocation and other commercial terms under the agreement, Magentas strategy and business plan, the future development, manufacture and commercialization between Beam and Magenta as well as statements regarding expectations and plans for the anticipated timing of Magentas clinical trials and regulatory filings and the development of Magentas product candidates and advancement of Magentas preclinical programs. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation, risks set forth under the caption Risk Factors in Magentas most recent Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission, risks, uncertainties and assumptions regarding the impact of the COVID-19 pandemic to Magentas business, operations, strategy, goals and anticipated timelines, and risks, uncertainties and assumptions inherent in preclinical and clinical studies, including, without limitation, whether results from preclinical studies or earlier clinical studies will be predictive of the results of future trials and the expected timing of submissions for regulatory approval or review by governmental authorities. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

Beam Forward-Looking Statements

This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including statements about the timing, progress and success of the collaboration contemplated under the agreement between Beam and Magenta, the successful evaluation of MGTA-117 in conjunction with Beams base-editing therapies under the agreement, the expected timing of filing INDs applications and the therapeutic applications of Beams technology. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in development and potential commercialization of our product candidates; Beams ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; whether preclinical testing of our product candidates and preliminary or interim data from preclinical and clinical trials will be predictive of the results or success of ongoing or later clinical trials; that enrollment of clinical trials may take longer than expected; that Beams product candidates will experience manufacturing or supply interruptions or failures; that Beam will be unable to successfully initiate or complete the preclinical and clinical development and eventual commercialization of product candidates; that the development and commercialization of Beams product candidates will take longer or cost more than planned; the impact of COVID-19 on Beams business and the other risks and uncertainties identified under the heading Risk Factors and in Beams Annual Reports on Form 10-K for the year ended December 31, 2019 and in Beams Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, and in any subsequent filings with the Securities and Exchange Commission. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release. Factors or events that could cause Beams actual results to differ may emerge from time to time, and it is not possible for Beam to predict all of them. Beam undertakes no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable law.

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Magenta Therapeutics and Beam Therapeutics Announce Collaboration to Evaluate Targeted Antibody-Drug Conjugate (ADC) MGTA-117 as Conditioning Regimen...

Human Behavior

AI: The complex solution to simplify health care – Brookings Institution

Health care languishes in data dissonance. A fundamental imbalance between collection and use persists across systems and geopolitical boundaries. Data collection has been an all-consuming effort with good intent but insufficient results in turning data into action. After a strong decade, the sentiment is that the data is inconsistent, messy, and untrustworthy. The most advanced health systems in the world remain confused by what theyve amassed: reams of data without a clear path toward impact. Artificial intelligence (AI) can see through the murk, clear away the noise, and find meaning in existing data beyond the capacity of any human(s) or other technology.

AI is a term for technologies or machines that have the capability to adapt and learn. This is the fundamental meaning of being data-driven, to be able to take measure of available data and perform an action or change ones mind. Machine Learning is at the heart of AIteaching machines to learn from data, rather than requiring hard-coded rules (as did machines of the past).

No domain is more deserving of meaningful AI than health care. Health care is arguably the most complex industry on earthoperating at the nexus of evolving science, business, politics, and mercurial human behavior. These influences push and pull in perpetual contradiction.

Health carespecifically psychologyis the mother of machine learning. In 1949, Dr. Donald Hebb created a model of brain cell interactions, or synaptic plasticity, that forms the ancestral architecture of the artificial neural networks that pervade AI today. Math to explain human behavior became mathematics to mimic and transcend human intellect. AI is now at the precipice of a return to the health care domain.

To achieve impact at scale, machine learning must be deployed in the most and least advanced health systems in the world. Any decent technology should remain resilient outside the walls of academia and the pristine data environments of tech giants. AI can learn from many dimensions of dataphotographs, natural language, tabular data, satellite imageryand can adapt, learning from the data thats available. The ability to adapt is what defines AI. AI at its best is designed to solve complex problemsnot wardrobe preferences. Now is the time to bring AI to health care.

COVID-19 is the greatest global crisis of our time: an immediate health challenge and a challenge of yet unknown duration on the economic and psychological well-being of our society. The lack of data-driven decisionmaking and the absence of adaptive and predictive technology have prolonged and exacerbated the toll of COVID-19. It will be the adoption of these technologies that helps us to rebuild health and society. AI has already forged new solutions for the COVID-19 response and the accelerated evolution of health care. Machine learning models from MIT for transmission rates have generated impressive precisionin some cases reducing error rates by 70 percent. Researchers at Mount Sanai in New York City have demonstrated the ability to reduce testing from two days to near instant by combining AI models with chest computed tomography (CT), clinical symptoms, exposure history, and laboratory testingreducing error of false negatives. AI modelsunlike test kitscan travel instantly to new users, are not limited in production, and do not require additional training and complementary equipment.

Adoption of AI must be done in concert with existing systems and solutions. Epidemiological models in concert with AI technology adapt and learn in real timeintegrating new data to help explain ancillary elements of health outcomes. However, collaboration between epidemiology and machine learning has been limited. The prominent epidemiological models are not integrating dynamic machine learning. Without machine learning, epidemiological models are updated weekly, losing precious time and rendering wildly inaccurate predictions that have been widely criticized. Human bias is writ large in these modelsvariable importance is determined by experts rather than learned and derived from the data.

AI models can derive implicit and explicit features from available data to increase the precision and adaptability of transmission predictions. Organizations like Metabiota have mapped thousands of pandemics to generate a model for risk. Existing electronic information systems (EIS) hold valuable historical health data when they are availableboth pandemic models and EIS are excellent sources for AI engines targeted at optimization of pandemic response at scale.

Optimizationin terms of tuning a health system to produce a maximum value (life expectancy, for example) or minimum value (cost of care) is the end goal of AI for health. By looking forward into the future and predicting demand, constraints, and behavior, AI can buy time. Time to prepare and ensure that resources are deployed to maximize the impact of every unit: financial, human, or commodity. Most models look backwardslike driving a car by only looking at the rearview mirroryet they are asked to make decisions for the future. Its Sisyphean to ask legacy analytics to prepare for tomorrow based on what is often a distant (months, weeks, or days at best) past of linear data inputs. Optimization through machine learning and AI technologies brings the prescience to data-driven decisions and actions required for impact. Machine-learning-optimized laboratory testing at MIT has accelerated discovery of new antibiotics previously considered unachievable due to the significant time and financial investment.

At the health system level, action is being accelerated through direct engagement with those at the front lines. Human-in- the-loop (HIL) machine learning (ML) is the process of receiving data-rich insights from people, analyzing them in real time, and sharing recommendations back. HIL ML is the science of teaching machines to learn directly from human input. In Mozambique and slated to expand to Sierra Leone, macro-eyes technology is learning directly from front-line health workersthe foremost experts on the conditions for care in the communities they serve. This becomes a virtuous cycle of high-value data, timely insights, and accelerated engagement at the point of care. Facility-level precision from HIL ML in Sierra Leone will complement AI optimization engines being deployed to probabilistically estimate the availability of essential resources at facilities across the country, account for new resources constraints, and recommend distribution of resources.

COVID-19 has highlighted the need for rapid connection between data analytics and the front lines of care. That connection still does not exist at scale. The result: Authorities must decipher a myriad of models estimating COVID-19-related transmissions and deaths in the near past and estimations for the future that dont build knowledge or data from the ground up. This fundamental disconnect has hindered health care for decadesthose who deliver the care have the least voice in how care is delivered. It can be resolved with minimal disruption using HIL ML to engage an educated and impassioned community of health workers.

AI in health has been successful but far too limited. The inability to trust what we dont fully understand, misrepresentation of AI expertise by early participants, and the financial fortitude of the global funding mechanisms remain barriers to adoption. AI canand willexponentially improve the delivery of care around the world. The data and the data infrastructure are ready and the time for bold investment is now. Investment must move away from pilots with insufficient horizon and commitment. AI at scaleas bold innovations of the pastwill only be possible with a committed corpus of financiers, policymakers, and implementing partners dedicating resources to AI experts solving problems at the foundations of health.

But we must proceed with caution. The world is replete with AI solutions and experts purporting to save the planet. Be criticalthere is very little real AI talent, and even fewer teams have the chops to deploy AI in the real world. The AI scientists of the future will not look like those of the recent past. The software engineers turned AI experts who brought AI to the digital world in Silicon Valley, and academics building models in protected vaults, will be usurped by adaptive, scrappy, problemsolving engineers using AI to make change in the communities they care about: deploying in the physical world meaningful solutions to complex problems. What is more meaningful than health?

Excerpt from:
AI: The complex solution to simplify health care - Brookings Institution

Human Behavior

Human behavior ‘is driving this’: Disturbing increase in number of hospitalizations due to COVID-19 in Houston area – KHOU.com

The Texas Medical Center says hospitalizations give an objective view of how COVID-19 impacts the healthcare system.

HOUSTON Doctors are concerned about Houston and Harris County's rising rate of hospitalizations of people suffering from COVID-19 in the last three weeks.

Houston Health Authority Doctor David Persse said simply speaking can spread the virus, so wearing a mask is critical.

People who dont yet have symptoms, thats actually when they spread the virus the most. Right in the couple of days before they have symptoms is when theyre most dangerous to the people near them," Dr. Persse said.

He, and doctors at UT Health, say the re-opening of the economy is likely one cause of the increased spread.

They say the percentage of people testing positive for COVID-19 is higher now than it was a few months ago.

Doctors say if you go out in public, the combination of wearing a mask and keep physical distance is the best way to stay safe. While doctors agree that being outside mitigates the spread, it is not a substitute for physical distancing.

Its really human behavior thats driving this," said Dr. Catherine Troisi, an infectious disease expert for UT Health.

Harris County Judge Lina Hidalgo released a new coronavirus "public threat level system," to help residents better understand the status of coronavirus in the area and what actions they need to take to help maintain the spread of the virus.

Dr. Troisi said limiting social circles to a select group of fewer than 10 friends people who you know have all been taking the same precautions is one of the safest ways to get together with friends, adding you are only as safe as the weakest link in your chain of friends.

Make that your household, your pod that you feel safe socializing with those people," Dr. Troisi said.

Dr. Persse said activities such as going out for brunch with people who live outside of your household can be risky.

Those are the exact types of behaviors the virus is going to take advantage of," Dr. Persse said. If youre out in public, you should be wearing a mask. Period.

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Human behavior 'is driving this': Disturbing increase in number of hospitalizations due to COVID-19 in Houston area - KHOU.com

Human Behavior

Leadership Advisory Firm ghSMART is Named on Forbes List of America’s Best Management Consulting Firms for 2020, Celebrates 25-year Anniversary -…

CHICAGO, June 16, 2020 /PRNewswire/ --ghSMART & Company has been named to the Forbes list of America's Best Management Consulting Firms for the fourth consecutive year. In 2020, Only 222 firms made this list out of 774,100 firms. That is fewer than 3 out of 10,000 firms, or .03%.

Dr. Geoff Smart, chairman and founder of ghSMART said, "I founded ghSMART 25 years ago on this day, for two main reasons. First, I wanted there to be a firm for wildly talented and good-hearted people to do meaningful work in the area of leadership and management, and to have a life outside of work. Second, I wanted influential leaders who run or own large organizations to use our expertise in human behavior to build valuable and successful organizations."

Randy Street, ghSMART's managing partner, said, "We are pleased and grateful that the ratings from clients and industry peers placed us on the Forbes list once again. It is a testament to the strength of our team and their ability to help leaders hire and develop talented teams with confidence."

In addition to consulting, ghSMART is known for publishing some of the top-selling and most-acclaimed books in the field of leadership. The firm published the New York Times bestseller Who: The A Method for Hiring (Smart & Street), The Wall Street Journal bestseller Power Score: Your Formula for Leadership Success (Smart, Street, and Foster), and the New York Times bestseller The CEO Next Door: The 4 Behaviors That Transform Ordinary People into World-Class Leaders (Botelho & Powell).

Elena Botelho, one of ghSMART's longest-serving partners, commented, "We believe that leadership is the ultimate lever for good in the world. It is exciting to see how far ghSMART has come in the past 25 years, and we are driven to continue to expand our impact globally with leaders of companies large and small, not-for-profits, governments, and non-governmental organizations."

About ghSMART: ghSMART is a leadership advisory firm, founded in 1995. The firm's Credo begins, "We exist to help leaders to amplify their positive impact on the world." Harvard Business School published two case studies on the firm as a pioneer in its industry. In 2020, Vault named ghSMART the #1 best company to work for in its industry, in overall satisfaction. The firm currently has a 4.9/5.0 rating on Glassdoor. For more information about ghSMART, please visit: http://www.ghsmart.com.

About the ForbesList of America's Best Management Consulting Firms:According to its website, Forbes'list of America's Best Management Consulting Firms is compiled by surveying 7,500 partners and executives of management consultancies, as well as 1,000 senior executives who worked with such firms over the last four years.

ContactMs. Mandy BartelsOffice of the ChairmanghSMART & Company, Inc. Tel. 224.444.8906[emailprotected]www.ghsmart.com

SOURCE ghSMART

ghsmart.com

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Leadership Advisory Firm ghSMART is Named on Forbes List of America's Best Management Consulting Firms for 2020, Celebrates 25-year Anniversary -...