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Immunology

Dragons of immunology | Opinion – Chemistry World

Since everyone is being forced these days to think about immunology, lets consider it in terms of chemistry and drug discovery. You can get two very different perspectives based on where you stand. From one view, inflammation and immune response might look like a wonderfully productive area for small molecules. Aspirin, dexamethasone, ibuprofen, hydrocortisone there are classic drugs that work on and near these pathways and have been used successfully by uncounted millions of patients. In the modern era, the list of best-selling prescription drugs prominently features antibodies and fusion proteins aimed at immunologic targets such as TNF-alpha and CD20, as treatments for inflammatory diseases from rheumatoid arthritis to cancer.

But from another vantage point, the whole field is full of trap doors, dead ends, and irritable dragons. Dexamethasone and other such steroids have such powerful effects (and powerful side effects) that they have to be administered carefully and for short periods. Thats why compounds such as ibuprofen were hailed as being anti-inflammatories that (good news!) werent steroids. The list of potential side effects for those antibodies is also long and impressive. To pick a particularly dramatic example that many will recall, a 2006 attempt by TeGenero to create a super-agonist for the T-cell receptor CD28 led to catastrophic effects in the Phase 1 volunteers, many of whom barely survived the initial dose.

Thats what the immune system has to offer: tremendous power, but power that can be aimed in all sorts of directions. And because immunology itself is so wildly, insanely complicated, there are a bewildering number of potential targets to think about. Were looking at hundreds of millions of years of evolutionary tinkering; there are layers upon layers of tangled, interlocking signaling pathways and mechanisms. Theres the innate immune system always on but rather nonselective and the adaptive system that features a gigantic combinatorial chemical library of antibodies that we all carry around with us for our entire lives slower to get going, but capable of feats of recognition that we still have trouble matching in the laboratory. Those aeons of evolution have been a walk down the narrow path between too little activity, opening the door to fatal infections, and too much, leading to autoimmune syndromes and responses to an infection that are worse than the disease itself. Its little wonder that the systems are encrusted with regulatory loops, flywheels, and gear-shifting mechanisms.

As usual, most of what drug discovery has to offer is an assortment of grit, sand, and spanners to throw into this apparatus. We are far, far better at shutting particular enzymes and receptors down than we are in turning any particular signal up. When you do see a drug mechanism that enhances some sort of activity, odds are good that it works by inhibiting something else that was in turn suppressing the desired target. A great number of interesting ideas in the field dont seem to be amenable to small-molecule manipulation at all, which is where those antibodies come in. The requisite binding sites can be too large and the selectivity needed to target them may be too great for anything other than a good-sized protein to have a chance.

Thats meant that immunology has been a proving ground for new therapeutic ideas and new modes of action. Monoclonal antibodies and fusion proteins are just the beginning. Mechanisms targeting protein expression, intra- and extracellular localisation, degradation, and the intricate varieties of post-translational modification are all highly relevant to immune and inflammation pathways. Add in the number of genetic immunological problems that can occur in the population, which would be targets for gene therapy or RNA mechanisms, and you have the whole range of cutting-edge drug research being brought in.

Most of these are too early in the process to be of likely use against the Covid-19 pandemic, of course. But we are learning a great deal about immunology very quickly under these conditions, with the huge efforts going into characterising the pathogen; treating the overactive immune response to it; and developing antibodies and vaccines against it. Well come out of this, and well come out of it with more tools and more knowledge than when we went in all acquired at a faster pace than we ever would have achieved otherwise. Lets take the benefits where we can find them!

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Dragons of immunology | Opinion - Chemistry World

Immunology

What’s the answer to slowing the spread of COVID-19 for older adults? – Aspen Times

Theres a lot of stupid floating around out there.

Thats what South Carolina Gov. Henry McMaster said during a recent news conference in which he pleaded with the public to make better decisions to slow the spread of COVID-19.

Thats the best quote ever its how you explain the recent surge (in cases), said Dr. Michael Schmidt, PhD, a professor of microbiology and immunology at the Medical University of South Carolina.

Dr. Schmidt is the guest host of an upcoming webcast, How Colorado Can Work Smarter to Slow the Spread of COVID-19 in Older Adults, presented by Renew Senior Communities. Renew CEO Lee Tuchfarber is co-hosting.

This is a plague for which the human race has a choice, Dr. Schmidt said. We already know how to stop this virus dead in its tracks.

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Much of the discussion will focus on how we can do our part as a society to slow the spread, but Dr. Schmidt will also discuss promising light at the end of the tunnel. From the potential that oral polio vaccines can safely and cheaply protect the U.S. population to excitement over bluetooth technology expanding the efficiency of contact tracing, Dr. Schmidt said various stop-gap measures could make a big difference until theres a COVID-19 vaccine.

The only thing more infectious than this virus is hope, he said.

Personal responsibility

The way we control the virus is really straightforward, Dr. Schmidt said its hygiene.

Wearing a mask to protect others, washing your hands and keeping a physical distance of at least six feet from other people are the most effective safety precautions.

If weve learned one thing, there are a lot of folks out there who are infected and dont know it, he said. The mere act of speech actually can spread the virus. So, if youre out carrying your business and talking, wear a mask.

Physical distancing is your only hope if youre not wearing a mask. The hope being that the virus dissipates in the air before smashing into your face.

Many medical folks are wearing face shields because the virus can come in from your tear ducts, Dr. Schmidt said.

As for hand hygiene, simple soap and water is all you need. The Centers for Disease Control and Prevention recommends washing hands for at least 20 seconds.

Strict safety protocols have proven to work at Renew Senior Livings two communities in Aurora and Glenwood Springs. Tuchfarber said all residents at both communities have remained COVID-free while a great number of the senior living facilities in Colorado have experienced outbreaks.

Renew put various safety measures in place for staff before they enter the building, and theyve even provided staff with meals to take home to their families to decrease their need to go to the grocery store. Much of this decision-making is data-driven, with various phases of safety measures implemented depending on the R-naught (Ro), which is the estimate of the number of people to whom each infected person spreads the virus.

Theres an inherent spreadability of the virus itself, but theres also an environmental factor, Tuchfarber said. So behavior can really affect the Ro.

What: How Colorado Can Work to Slow the Spread of COVID-19 for Older Adults, a webcast talk series presented by Renew Senior Communities.

When: Wednesday, July 1, 3 to 4 p.m.

Where: Register for free at renewsenior.com.

Featured co-host: Dr. Michael Schmidt, PhD, is a professor of microbiology and immunology at the Medical University of South Carolina. He is a well-published expert in the area of

infectious disease control and pandemics. He ran the American Society for Microbiology

and set its research priorities for vaccines and testing. He hosts a podcast called, This

Week in Microbiology. Dr. Schmidt is an advisor to MicrogenDx, the second largest next

generation testing lab in the U.S.

Testing

Testing serves a vital role in understanding and controlling the spread of COVID-19, Dr. Schmidt said. He points to data from Taiwan, a densely populated island that has managed to keep its number of confirmed cases of COVID-19 to date to less than 450 thanks to aggressive testing and contract tracing.

Going forward, given that we know there is significant asymptomatic and presymptomatic transmission of the virus, pre-emptive testing may be a way we help slow the spread of the virus in areas that have suddeningly seen a surge in an increase in new cases, he said. Simply, local areas may wish to routinely screen random members within their community looking for an up-turn in the number of cases. Such a program will be especially important to companies with public-facing employees, so that they can ensure that their employees and customers are as safe as possible.

Renew is working on a strategy for preemptive testing rather than waiting for a positive case and then reacting to it. Tuchfarber said Renew should be implementing that new protocol very soon.

Preemptive testing of all staff on a regular basis, unprompted by a positive test result, is presently a rarity in our industry, but is an important measure to assure safety. We are preparing to integrate this program in our COVID-19 safety regimen, Tuchfarber said. This is an extra measure of safety that we feel strongly about taking.

Facilitating a global response

In an effort to facilitate a global response, scientists are looking at three strategies: diagnostics, therapeutics and vaccines.

Diagnostics essentially look at how we can slow the spread faster and better, while therapeutics focus on the use of drugs.

If were going to restart the economy, we need two to three drugs so the virus doesnt adapt to the drugs like it did with HIV and hepatitis C in the 1980s, Dr. Schmidt said.

Vaccines are the area for which Dr. Schmidt is truly excited. There are more than 90 candidate vaccines currently being studied, with microbiologists, structural biologists, physiologists and others all pulling in the same direction.

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What's the answer to slowing the spread of COVID-19 for older adults? - Aspen Times

Immunology

Cause of Common Autoinflammatory Disease May Have Protected Ancestors From Plague – Technology Networks

Researchers have discovered that Mediterranean populations may be more susceptible to an autoinflammatory disease because of evolutionary pressure to survive the bubonic plague. The study, carried out by scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, determined that specific genomic variants that cause a disease called familial Mediterranean fever (FMF) may also confer increased resilience to the plague.

The researchers suggest that because of this potential advantage, FMF-causing genomic variants have been positively selected for in Mediterranean populations over centuries. The findings were published in the journal Nature Immunology.

Over centuries, a biological arms race has been fought between humans and microbial pathogens. This evolutionary battle is between the human immune system and microorganisms trying to invade our bodies. Microbes affect the human genome in many ways. For example, they can influence some of the genomic variation that accumulates in human populations over time.

"In this era of a new pandemic, understanding the interplay between microbes and humans is ever critical," said Dr. Dan Kastner, NHGRI scientific director and a co-author on the paper. We can witness evolution playing out before our very eyes.

One such microbe is Yersinia pestis, the bacterial agent responsible for a series of well-documented bubonic plague(link is external) epidemics that led to over 50 million deaths.

FMF, like the plague, is an ancient disease. It is the most common periodic fever syndrome, and symptoms of FMF include recurrent fevers, arthritis, rashes and inflammation of the tissues that line the heart, lungs, and abdominal organs. FMF may also lead to renal failure and death without treatment. The disease appears across the Mediterranean region and mostly affects Turkish, Jewish, Armenian and Arab populations.

Genomic variants in the MEFV gene cause FMF. MEFV encodes a protein called pyrin. In healthy people, pyrin plays a role in the inflammatory response of the body. Pyrin is activated when there is an immune response (for example, in the event of an infection). Pyrin increases inflammation and the production of inflammation-related molecules.

In contrast, FMF patients produce abnormal pyrin because of genomic variants (mutations) in the MEFV gene. Mutated pyrin does not need an infection or other immune trigger to be activated; rather, it is able to directly predispose people to seemingly unprovoked episodes of fever and inflammation.

The MEFV mutations also have other usual properties. Researchers have discovered that people with only one copy of a MEFV genomic variant that causes FMF do not get the disease. Also, prior to effective treatment, those with two copies have high mortality rate by the age of 40, but usually live long enough to have children.

Despite the lower survival rate, almost 10% of Turks, Jews, Arabs and Armenians carry at least one copy of an FMF-causing genomic variant. If chance were the only factor, that percentage would be much lower.

The researchers proposed that this higher percentage was a consequence of positive natural selection, which is an evolutionary process that drives an increase in specific genomic variants and traits that are advantageous in some way.

"Just like sickle cell trait is positively selected for because it protects against malaria, we speculated that the mutant pyrin in FMF might be helping the Mediterranean population in some way," said Jae Jin Chae, Ph.D., senior author of the paper and a staff scientist in NHGRI's Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch. "The mutant pyrin may be protecting them from some fatal infection."

The team turned to Yersinia pestis, the infamous bubonic plague-causing bacterium, as a possible candidate for driving the evolutionary selection for FMF mutations in the Mediterranean population.

It turns out Yersinia pestis contains a particular molecule that represses the function of pyrin in healthy individuals. In doing so, the pathogen suppresses the body's inflammatory response to the infection. This way, the body cannot fight back.

"Inflammation is a process in which white blood cells protect the body from infection. From the host's point of view, inflammation helps us survive. From the bacteria's point of view, inflammation is something to be evaded by any means available," said Daniel Shriner, Ph.D., staff scientist in the Center for Research on Genomics and Global Health at NHGRI.

Researchers were struck by the fact that Yersinia pestis affects the very protein that is mutated in FMF. They considered the possibility that FMF-causing genomic variants may protect individuals from the bubonic plague caused by Yersinia pestis.

The idea that evolution would push for one disease in a group to fight another may seem counterintuitive. But it comes down to what is the least bad option.

The average mortality rate of people with bubonic plague over centuries has been as high as 66%, while, even with a carrier frequency of 10%, less than 1% of the population has FMF. Theoretically, the evolutionary odds are in the latter's favor.

But first, the team had to verify if two of the genomic variants that cause FMF had indeed undergone positive selection in Mediterranean populations.

For this, they performed genetic analysis on a large cohort of 2,313 Turkish individuals. They also examined genomes from 352 ancient archaeological samples, including 261 from before the Christian era. The researchers tested for the presence of two FMF-causing genomic variants in both groups of samples. They also used population genetics principles and mathematical modeling to predict how the frequency of FMF-causing genomic variants changed over generations.

"We found that both FMF-causing genomic variants arose more than 2,000 years ago, before the Justinian Plague and the Black Death. Both variants were associated with evidence of positive selection," said Elaine Remmers, Ph.D., associate investigator in NHGRI's Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch.

Researchers then studied how Yersinia pestis interacts with FMF-causing genomic variants. They took samples of particular white blood cells from FMF patients. In addition, they took samples from people who carry just one copy of the genomic variants (hence, do not get the disease).

The team found that Yersinia pestis does not reduce inflammation in white blood cells acquired from FMF patients and people with one copy of FMF-causing genomic variants. This finding is in stark contrast to the fact that Yersinia pestis reduces inflammation in cells without FMF-associated mutations.

The researchers thought that if Yersinia pestis does not reduce inflammation in people with FMF, then perhaps this could potentially increase patients' survival rate when infected by the pathogen.

To test this hypothesis, the researchers genetically engineered mice with FMF-causing genomic variants. They infected both healthy and genetically engineered mice with Yersinia pestis. Their results showed that infected mice with the FMF-causing genomic variant had significantly increased survival as compared to infected healthy mice.

These findings, in combination, indicate that over centuries, FMF-causing genomic variants positively selected in Turkish populations play a role in providing resistance to Yersinia pestis infection. Whether the same is true for other Mediterranean populations remains to be seen. The study offers a glimpse into the unexpected and long-lasting influence of microbes on human biology.

ReferencePark, Y.H., Remmers, E.F., Lee, W. et al. Ancient familial Mediterranean fever mutations in human pyrin and resistance to Yersinia pestis. Nat Immunol (2020). https://doi.org/10.1038/s41590-020-0705-6.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cause of Common Autoinflammatory Disease May Have Protected Ancestors From Plague - Technology Networks

Immunology

Postdoctoral Positions in Inflammatory Bowel Diseases and Tumor – Nature.com

Postdoctoral Positions in Inflammatory Bowel Diseases and Tumor Immunology

Two postdoctoral training positions are available in the laboratory of Hans-Christian Reinecker MD, in the Department of Internal Medicine, the Division of Digestive and Liver Diseases and Division of Immunology at UT Southwestern Medical Center to study the role of genetic variants associated with inflammatory bowel diseases on mechanisms of inflammation, tumorigenesis and anti-microbial host defenses. Focus is on new mechanisms of innate immune recognition for viral and bacterial pathogens and control of dendritic cells, macrophages and T cells. Our laboratory offers opportunities in these projects:

1. Target intracellular microtubule based microbial pattern recognition to control disease mechanisms of Inflammatory Bowel Diseases.2. Control of adaptive host-defenses by Schlafen family proteins.3. Controlling innate and adaptive immune responses by Sensor Stimulator of Interferon Genes (STING) mediated microbial recognition.4. Developing strategies to induce anti-tumor immunity for cancer immunotherapy.

Candidates must hold a Ph.D. and/or M.D. Degree. Experience in Immunology, Oncology or Microbiology in addition to a solid foundation in molecular and cell biology is required. Prior experiences in protein mutagenesis, gene targeting approaches or biochemistry is preferred. Prior work leading to publication in peer-reviewed journals is recommended.

Information on our postdoctoral training program and benefits can be found in our Postdoc Handbook or at http://www.utsouthwestern.edu/postdocs.

Interested individuals should send a CV, statement of interests, and a list of three references to:

Hans-Christian Reinecker, M.D.UT Southwestern Medical Center5323 Harry Hines Blvd.Dallas, TX 75390-9151Hans-Christian.Reinecker@UTSouthwestern.edu

UT Southwestern Medical Center is an Affirmative Action/Equal Opportunity Employer. Women, minorities, veterans and individuals with disabilities are encouraged to apply.

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Postdoctoral Positions in Inflammatory Bowel Diseases and Tumor - Nature.com

Immunology

New Research: Lessons from immune response of most severe Covid patients – The Indian Express

By: Express News Service | New Delhi | Updated: June 30, 2020 12:52:42 am Coronavirus test kits. T cells work alongside antibodies in trying to clear the virus and stopping the infection. (AP Photo: David J. Phillip)

A new study has found that even the sickest Covid-19 patients produce T cells that help fight the virus. T cells are a key component of the immune system and their roles include killing infected host cells, activating other immune cells, and regulating the immune response. The study cites its findings as further evidence that a Covid-19 vaccine (whenever developed) will need to elicit T cells to work alongside antibodies.

The new research was published in the journal Science Immunology on Friday.

The researchers followed 10 severely ill Covid-19 patients who were on ventilators at Erasmus University Medical Center, Netherlands. Two of the patients eventually died. An in-depth look at their immune system responses showed that all 10 patients produced T cells that targeted the SARS-CoV-2 virus. These T cells worked alongside antibodies in trying to clear the virus and stopping the infection.

The researchers note that these findings are in line with a recent study, published in Cell, that showed a robust T cell response in individuals with moderate cases of Covid-19. In both studies, the T cells in these patients prominently targeted the spike protein on SARS-CoV-2, according to La Jolla Institute for Immunology, researchers from which are involved in both studies. It is the spike protein that the coronavirus uses to enter human cells. The new study adds to growing evidence that the spike protein is a promising target. Accroding to La Jolla, it also confirms that the immune system can also mount strong responses to other targets on the virus.

This is good news for those making a vaccine using spike, and it also suggests new avenues to potentially increase vaccine potency, researcher Daniela Weiskopf, first author of the new study, said in a statement.

While the Cell paper followed San Diego residents, the new paper follows Dutch patientsand the T cell responses were consistent in both populations. This study is important because it shows this immune response in patients thousands of miles apart. The same observation has now been strongly reproduced in different continents and different studies, Weiskopf said.

Source: La Jolla Institute for Immunology

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New Research: Lessons from immune response of most severe Covid patients - The Indian Express

Immunology

High fiber diet may improve the quality of life for patients with ulcerative colitis – News-Medical.Net

Eating diets low in fat and high in fiber may improve the quality of life of patients with ulcerative colitis (UC) -; even those in remission.

That's the finding of a study published in Clinical Gastroenterology and Hepatology led by Maria T. Abreu, M.D., professor of medicine and professor of microbiology and immunology at the University of Miami Miller School of Medicine.

Patients with inflammatory bowel disease always ask us what they should eat to make their symptoms better. Sadly, there have been very few really good studies that provide that information."

Maria T. Abreu, M.D., Professor and Director, Department of Medicine, University of Miami Miller School of Medicine

Dr. Abreu's work is changing that.

The current study looked at 17 people with UC, a type of inflammatory bowel disease (IBD) that can cause a number of symptoms, including bloody diarrhea, abdominal cramps and pain.

Each participant's UC was either in remission or considered mild, with relatively little diarrhea, bleeding, or pain.

All foods were catered and delivered to participants' homes.

Researchers looked at the participants' pre-study diets and used questionnaires to measure their quality of life based on their physical, social and emotional well-being.

The questionnaires were given at the study's start and four weeks after being on each diet.

Participants also underwent blood and stool tests during the same period to look for markers of inflammation and to check the balance of their gut bacteria and metabolites, something that can impact digestive health.

"The results were fascinating and show us how poorly patients eat at baseline," said Dr. Abreu, who is also director of the University of Miami Health Systems Crohn's and Colitis Center.

Perhaps more important, they showed that improving one's diet could improve their overall well-being. Both the low-fat and high-fat diets had more fruits and vegetables and fiber than the patients' baseline diets.

Both study diets were well tolerated and resulted in better quality of life for the study subjects compared to baseline diets, which were significantly unhealthier.

However, on the low-fat diet, participants also had lower levels of inflammation and signs of improvement in bacterial imbalance in the gastrointestinal tract.

Sadly, many patients with ulcerative colitis are told to avoid fruits and vegetables, which seem to be very beneficial.

The findings suggest that dietary interventions could benefit patients with UC in remission and, perhaps, other forms of IBD as well.

"We are now testing a similar diet in Crohn's disease patients but adding a psychological component to help with long-term adherence to a healthy diet," said Dr. Abreu.

Source:

Journal reference:

Fritsch, J., et al. (2020) Low-fat, High-fiber Diet Reduces Markers of Inflammation and Dysbiosis and Improves Quality of Life in Patients With Ulcerative Colitis. Clinical Gastroenterology and Hepatology. doi.org/10.1016/j.cgh.2020.05.026.

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High fiber diet may improve the quality of life for patients with ulcerative colitis - News-Medical.Net

Immunology

Researchers look at benefits MMR booster shot could have on COVID-19 – Wink News

WINK NEWS

As concerns for coronavirus infections continue, a pair of medical researchers say one way to escape the worst of the virus is already here.

We spoke to researchers, a Lee Health doctor and other medical experts Thursday about the benefits of getting an MMR booster shot in relation to COVID-19.

Very suddenly, we were seeing nobody, and it came to the point we had to close this office, said Dr. Thomas Shiller, a pediatrician at Lee Health. Normally, wed be giving vaccines during that time, and they werent happening.

Once the pandemic began, Schiller says childhood vaccinations plummeted.

But a new scientific theory says those vaccinations could be the key to helping everyone avoid the worst of the virus. And COVID-19 infection rates in children, or the lack thereof, lead the way.

The earliest data coming out of China with [COVID-19] nobody under the age of nine died, said Mairi Noverr, a Tulane professor with a Ph.D. in microbiology and immunology. So I wondered whether that was because children get repeated live attenuated vaccines throughout childhood.

Noverr and Paul Fidel, an adjunct professor at LSU with a Ph.D. in microbiology, immunology & parasitology, said, between their animal trials and anecdotal stories, certain vaccines seem to prime the immune system.

These live attenuated vaccines in general provide something more than just the immunity to the target pathogens that they are made for, Fidel said. They provide this sort of added extra non-specific immunity and non-specific benefits for other types of infections.

Now, the health experts are recommending adults get an MMR booster shot.

I called it a no harm no foul type situation because, if were wrong, well you got some immunity to measles, mumps and rubella, Fidel said. If were right, you have that, plus you could be helping yourself if you ever got infected with [COVID-19].

Its an idea that local health leaders say needs more evidence.

Until we get into deep research and doing some studies and really trying it out in the laboratory and on people, were not going to be able to determine if this is true or not, said Rober Hawkes, the director of FGCUs physician assistant program.

And its and idea Noverr and Fidel agree with. They say theyre hoping to get clinical trials underway to test their theory.

We have to do the science, and its really important to do it and to get the data, Fidel said.

But for Schillers patients, it could be just one more reason to come in and get vaccinated.

I hadnt seen one of my patients get [COVID-19] up until the past couple of weeks, and now its happening left and right, and its a little disconcerting, Schiller said.

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Researchers look at benefits MMR booster shot could have on COVID-19 - Wink News

Cell Biology

The biotech IPO boom is becoming ‘historic’ as four more throw their hats in – Endpoints News

Four more US biotechs filed to go public Friday as yet more companies clamber to get through a yawning IPO window and onto a market thats signaled its willingness to reward nearly any new drugmaker.

The new entrants are led by ALX Oncology and the biological analytics biotech Berkeley Lights, each of whom filed to raise $100 million. The autoimmune company Pandion Therapeutics also filed for $75 million, and Kiromic Biopharma, a tiny immuno-oncology startup based in San Antonio, filed for $25 million.

These companies will try to capitalize on a 2020 biotech IPO boom that the investment firm Renaissance Capital recently called historic. The spree began in January and, after a brief interlude when the pandemic first hit the US and Europe, has only picked up in the last two months. The 23 companies that have gone public averaged an 80% return on their offering price, according to Renaissance Capital numbers. Every single one priced above their midpoint or upsized their offering.

Unlike most of their fellow newly or would-be public biotechs, Berkeley Lights will enter the market with significant revenue on the books. The company doesnt make drugs but instead has built a digital cell biology platform that can analyze living cells from a variety of different dimensions and, in principal, accelerate drug development. Theyve partnered with Sanofi and Pfizer on antibody discovery and last year, signed a $150 million pact with Ginkgo Bioworks to help the synthetic biology unicorn advance its genetic engineering capabilities.

All told, the company earned $51 million in revenue last year. Unlike a drug developer, they have no cash earmarked for specific pipeline products, and said they will use proceeds for research, potential acquisitions and general corporate purposes.

For ALX Oncology, a successful offering would mean their second $100 million tranche of the year. In February, the California biotech raised $105 million to help advance its sole pipeline candidate: an antibody designed to target CD-47. Thats the same dont-eat-me signal targeted by Irv Weissmans Forty Seven Inc., the biotech Gilead paid $5 billion for in January. ALXs pitch is that their antibodys FC receptor is engineered to not attract macrophages, reducing toxicity. The biotech will use their proceeds to push the drug through its ongoinghead and neck squamous cell carcinomaand gastric cancer trial and begin new trials for it in acute myeloid leukemia and myelodysplastic syndrome. A portion is also earmarked for CMC work.

Founded out of Polaris in 2018, Pandion Therapeutics was tapped last year for an up-to $800 million partnership to help a reorganizing Astellas develop antibodies for auto-immune disorders. That deal included $45 million upfront and the company also earned $80 million from a Series B in April. The new funding will be used to push their lead molecule through Phase I/II trials in ulcerative colitis while also backing preclinical research, particularly on a pair of antibodies meant to turn on the PD-1 checkpoint and tamp down the immune system.

Kiromic, meanwhile, is in part just trying to stay alive. With less than $2 million 5 million when a subsequent $3 million Series B is included in the bank at years end, they acknowledged in their S-1 that theres substantial doubt regarding the Companys ability to continue as a going concern. In this climate, though, thats worked out just fine for other companies. Applied Molecular Transport went publicin May with the same concerns. They ultimately raised $177 million.

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The biotech IPO boom is becoming 'historic' as four more throw their hats in - Endpoints News

Cell Biology

COVID 19 Impact On Global Cell And Tissue Analysis Products Market 2020 Analysis By Major Key Players | Danaher, Luminex, EMD Millipore Corporation,…

Cell And Tissue Analysis Products Industry Overview Competitive Analysis, Regional and Global Analysis, Segment Analysis, Market Forecasts 2026

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Cell Biology

If Biology Can Build It, They Will Come: Ginkgo Bioworks Is Laying The Foundation For The $4 Trillion Bioeconomy – Forbes

Early innovators in synthetic biology have had to get creative to grow not just their own ... [+] businesses, but the industry as a whole. Perhaps no company has contributed more to this growth than Ginkgo Bioworks.

Imagine there was a single method for making just about any product in the worldplastics, food, medicine, data storage devices, even a brain-computer interfaces. Now imagine that this method was faster, cheaper, and more sustainable than conventional manufacturing. Sounds like science fiction, right?

Its not science fiction: its synthetic biology, a field that uses biology as a manufacturing platform. Using the latest gene-editing techniques, synthetic biology can program yeast and bacteria into tiny cellular factories capable of making an endless range of products. Its also the driving force behind the $4 trillion bioeconomy, with great promise for building a more sustainable and abundant world.

Compared to sectors like pharmaceuticals and industrial chemicals, synthetic biology is relatively young. About 150 companies on Crunchbase describe themselves using the term synthetic biology, although SynBioBeta tracks more than 700 companies in the field. These early adopters either manufacture their own products with synthetic biology or provide synbio tools and technologies to help other companies transform the way they make things.

Early innovators in synthetic biology have had to get creative to grow not just their own businesses, but the industry as a wholeand perhaps few companies have contributed more to the industrys growth than Ginkgo Bioworks.

Ginkgo Bioworks is in a class of companies like Genomatica, Arzeda, Conagen, Zymergen, and Amyris AMRS that provides biotech infrastructure and servicesthe back-end of the synthetic biology industry. Rather than produce final products itself, Ginkgo designs and engineers microbes for a wide range of customer needs, from cannabinoid-producing bacteria to yeast that ferment next-generation food proteins.

Inside of Ginkgo Bioworks.

While Ginkgo believes that its microbes could one day produce virtually any physical good, most of Ginkgos would-be customers have relied for decades on traditional petrochemical or agricultural means of production. But Ginkgo isnt waiting for the slow, gradual adoption of synthetic biology by old-world players. Instead, its bringing its biology-based approach to the market by creating its own demand.

Already, Ginkgo has announced three spin-outs and strategic investments:

In February 2019 Ginkgo launched Motif Foodworks with a $90 million Series A, the largest in food tech history. This spin-out is using microbes to provide next-generation alternative proteins and other ingredients to food companies, showing the holistic view Ginkgo takes in the synthetic biology market. Ginkgo spun out Motif to develop and manufacture animal-free food ingredients, betting that plant-based meats and alternative dairy products would grow into a lucrative market. As part of this spin-out, a servicing agreement positioned Ginkgo as the provider of the microbes that Motif would use to manufacture its products.

Depending on the project, a subsidiary like Motif might have access to Ginkgos platform and technology at no cost. Alternatively, the investment may have dollars specifically earmarked for Ginkgos services, resulting in an immediate, new revenue-paying customer. Regardless of the initial financial arrangement, Ginkgo successfully created both a promising investment and a reliable future customer in one ambitious move.

Joyn Bio is a joint venture announced in March 2018 and funded to the tune of $100 million by agricultural giant Bayer, Ginkgo, and Viking Global Investors. The Joyn Bio venture carries technological benefits as well, with 100,000 of Bayers proprietary microbial strains being shared with Gingko. These strains can now be incorporated into Ginkgos internal metagenomics database. Even without explicit IP transfer, Ginkgo gets to flex its technological and commercial muscles in the context of a new industry.

In the pharmaceutical industry, Ginkgo has invested $80 million in its partner Synlogic, which will use Ginkgos cell programming platform to accelerate Synlogics pipeline of living medicines. Both companies believe that the ability to program living cells to sense and respond to treat complex diseases has great potential, possibly transforming the next generation of pharmaceuticals.

Aoife Brennan, Synlogic CEO

We have been working with Ginkgo for over two years now, said Aoife Brennan, Synlogic CEO. We initially started with a pilot project that went so well, we expanded our collaboration.

Brennan says Synlogic has really benefited as a company from working with Ginkgo. Having access to Ginkgos expertise and foundry services has allowed us to initiate more projects and to make sure that we are moving the best synthetic biotics into further development.

Brennan says that Ginkgo is not just a good collaborator, it also shares her companys values. Both of our companies share a passion for synthetic biology and making a positive impact on the world.

As Ginkgo seeks to attract customers in new markets, spin-outs and investments like Motif, Joyn Bio, and Synlogic demonstrate to other big players how synthetic biology is going to disrupt industries like food, agriculture, and pharmaand how synthetic biology can be used to transform their own businesses.

With this business model successfully piloted, Ginkgo has begun building a pipeline of promising biotech start-ups poised to be users of its microbial design platform. Partnering with start-up incubators Y Combinator and Petri, Ginkgo offers select start-ups access to its services in exchange for equity. The start-ups benefit from access to a technology stack that can save them large amounts of capital and time that would otherwise be sunk into building their own microbial design infrastructure.

Y Combinator partner Jared Friedman

"Ginkgo Bioworks was the first life sciences company YC funded, back in 2014, Y Combinator partner Jared Friedman told me. We believed early on that what they were building would help power the next generation of synbio startups, and it's been impressive to see them execute on that mission.

Friedman says that Ginkgo is making it cheaper and easier for new companies to get started by providing them with a platform that makes engineering biology easier.

We have a shared vision for the future, one in which bio startups are as easy to start as software startups, where founders don't have to spend years and millions of dollars booting up a genetic engineering lab, said Friedman. We're proud to be part of Ginkgo's continuing work to make this the standard."

Further enhancing this early pipeline of start-ups which rely on Ginkgos platform, the company recently announced the creation of a $350 million Ferment Fund. The Ferment Fund will spin out additional companies into promising markets identified by the Ginkgo team. Not only do these investments provide Ginkgo with a stake in promising biotech firms, but they also enable Ginkgo to support the growth of a synbio ecosystem reliant on its platform.

In a demonstration of the flexibility of the companys technology platform, as well as its commitment to help in the fight against the coronavirus, Ginkgo recently took several actions to help scale the research communitys response to the pandemic.

Ginkgo announced Concentric, a program to offer COVID-19 testing at scale to support schools and businesses in their reopening strategies. Concentric can provide end-to-end, on-site testing services for organizations that seek to make testing available to their communities.

Testing is essential for understanding and stopping the spread of the virus, Ginkgo said in an op/ed. By repurposing its next-generation sequencing capacity to rapidly scale testing, Ginkgo hopes to turn the tide.

In March, Ginkgo pledged $25 million of its research and development resources to help researchers battling the coronavirus. Ginkgo has used its DNA synthesis capabilities to make the viruss sequences freely available for use in R&D for diagnostics, therapeutics and vaccines. Ginkgo also is a part of a Berkeley Lights consortium for antibody discovery and testing, helping to scale up infrastructure for antibody lead optimization.

As synthetic biology start-ups grow, they will continue to lean on Ginkgos platform for microbial design, since developing in-house capabilities will appear increasingly redundant with each successful Ginkgo collaboration. In this way, Ginkgo will have created a robust ecosystem of companies modeled after its own Motif Foodworks, full of start-ups that excel at developing and biomanufacturing final products while they outsource their microbial design to the Ginkgo Bioworks mothership.

Follow me on Twitter at @johncumbers and @synbiobeta. Subscribe to my weekly newsletters on synthetic biology. Thank you to Matthew Kirshner for additional research and reporting in this article. Im the founder of SynBioBeta, and some of the companies that I write aboutincluding Ginkgo Bioworksare sponsors of the SynBioBeta conference and weekly digestheres the full list of SynBioBeta sponsors.

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If Biology Can Build It, They Will Come: Ginkgo Bioworks Is Laying The Foundation For The $4 Trillion Bioeconomy - Forbes