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30 Years of Developing a Messenger RNA Vaccine: What We Know So Far

Coronavirus vaccine: what we know so far – a comprehensive guide by academic experts

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2 years ago

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This article was originally published by The Conversation.

 
 
Since the early days of the pandemic, attention has focused on producing a vaccine for COVID-19. With one, it’s hoped it will be able to suppress the virus without relying purely on economically challenging control measures. Without one, the world will probably have to live with COVID-19 as an endemic disease. It’s unlikely the coronavirus will naturally burn itself out. With so much at stake, it’s not surprising that COVID-19 vaccines have become both a public and political obsession. The good news is that making one is possible: the virus has the right characteristics to be fended off with a vaccine, and the economic incentive exists to get one (or indeed several) developed. But we need to be patient. Creating a new medicine requires a large amount of thought and scrutiny to make sure what’s produced is safe and effective. Researchers must be careful not to allow the pressure and allure of creating a vaccine quickly to undermine the integrity of their work. The upshot may be that we don’t have a highly effective vaccine against COVID-19 for some time. Here, authors from across The Conversation outline what we know so far. Drawing upon their expertise, they explain how a COVID-19 vaccine will work, the progress a leading vaccine (developed by the University of Oxford with AstraZeneca) is making, and what challenges there will be to manufacturing and rolling a vaccine out when ready. How will vaccines work for COVID-19? How the spike protein is produced The benefits of different designs Why boosters may be needed What determines how we respond to vaccines Why vaccines provide strong immunity How to use a vaccine when it’s available How is the Oxford vaccine being developed, tested and approved? The many steps of vaccine development The results of phase 1 and phase 2 trials How the phase 3 trial will work Why testing was paused – and why we shouldn’t be alarmed Why vaccine makers need to be more open Why we need to know what’s in placebos How will the vaccine be made and rolled out? How to prepare enough vaccines for the whole world How tobacco could play a role in producing a vaccine Why vaccines need to be kept cold Will rich countries buy up the supply when vaccines are available? How to stop rich countries from depriving poorer ones Who should get a vaccine first? How do you counter resistance and scepticism? Vaccine hesitancy is nothing new Are anti-vaxxers that big a problem? How the far right is exploiting the pandemic How to build trust in vaccines

How will vaccines work for COVID-19?

Producing the spike protein

Although the way the body interacts with SARS-CoV-2 isn’t fully understood, there’s one particular part of the virus that’s thought to trigger an immune response – the spike protein, which sticks up on the virus’s surface. Therefore, the two leading COVID-19 vaccines both focus on getting the body to produce these key spike proteins, to train the immune system to recognise them and destroy any viral particles that exhibit them in the future.
Illustration of the SARS-CoV-2, showing the spike proteins on its surface
SARS-CoV-2, with its spike proteins shown in red. US Centers for Disease Control and Prevention/Wikimedia Commons

The pros and cons of different designs

The leading vaccines both work by delivering a piece of the coronavirus’s genetic material into cells, which instructs the cell to make copies of the spike protein. As Suresh Mahalingam and Adam Taylor explain, one (Moderna’s) makes the delivery using a molecule called messenger RNA, the other (AstraZeneca’s) using a harmless adenovirus. These cutting-edge vaccine designs have their pros and cons, as do traditional methods.

Boosters may be needed

The strongest immune responses, says Sarah Pitt, come from vaccines that contain a live version of what they’re trying to protect against. Because there’s so much we don’t know about SARS-CoV-2, putting a live version of the virus into a vaccine can be risky. Safer methods – such as getting the body to make just the virus’s spike proteins, or delivering a dead version of the virus – will lead to a weaker response that fades over time. But boosters can top this up.

What governs how we respond to vaccines?

A vaccine’s design isn’t the only factor that determines how strong our immune response is. As Menno van Zelm and Paul Gill show, there are four other variables that make each person’s response to a vaccine unique: their age, their genes, lifestyle factors and what previous infections they have been exposed to. It may be that not everyone gets long-lasting immunity from a vaccine.

Why vaccines provide strong immunity

If well-designed, a vaccine can provide better immunity than natural infection, says Maitreyi Shivkumar. This is because vaccines can focus the immune system on targeting recognisable parts of the pathogen (for example the spike protein), can kickstart a stronger response using ingredients called adjuvants, and can be delivered to key parts of the body where an immune response is needed most. For COVID-19, this could be the nose.
A woman receiving a nasal flu vaccine.
Nasally delivered vaccines are already in use for some diseases, such as flu. Douglas Jordan, MA/CDC

How to use a vaccine when it’s available

Scientists think between 50% and 70% of people need to be resistant to the coronavirus to stop it spreading. Using a vaccine to rapidly make that many people immune might be difficult, says Adam Kleczkowski. Vaccines are rarely 100% effective, and hesitancy and potential side effects may make a quick, mass roll-out unrealistic. A better strategy might be to target people most at risk together with those likely to infect many others.

How is the Oxford vaccine being developed, tested and approved?

The many steps of vaccine development

Vaccine development is quicker now than it ever has been, explain Samantha Vanderslott, Andrew Pollard and Tonia Thomas. Researchers can use knowledge from previous vaccines, and in an outbreak more resources are made available. Nevertheless, it’s still a lengthy process, involving research on the virus, testing in animals and clinical trials in humans. Once approved, millions of doses then need to be produced.

Phase 1 and phase 2 trials are successful

After showing promise in animals, the University of Oxford’s vaccine moved onto human testing – known as clinical trials, which are split into three phases. Here, Rebecca Ashfield outlines the joint phase 1 and 2 trial that the vaccine passed through to check that it was safe and elicited an immune response, and explains how the vaccine actually uses a separate virus – a chimpanzee adenovirus – to deliver its content into cells.

How the phase 3 trial works

Earlier trial phases showed that the vaccine stimulated the immune system, as expected. But the million-dollar question is whether this actually protects against COVID-19. Finding out means giving the vaccine to thousands of people who might be exposed to the coronavirus and seeing whether they get sick. As Ashfield and Pedro Folegatti show, this requires running vaccination programmes in countries across the world.

Testing was paused – and that’s OK

In September, the phase 3 trial of the Oxford vaccine was paused after a patient fell ill with a possible adverse reaction. Understandably this caused dismay, but it shouldn’t have, says Simon Kolstoe. Pauses like this are common, as independent moderators are needed to assess exactly what has happened. Often illnesses in trials are unrelated to what’s being tested. But even if they are, that’s exactly what we want these tests to show.
A person receiving an injection in their arm.
In the US arm of the trial, one-third of participants are receiving a saline injection as a control. DonyaHHI/Shutterstock

But vaccine makers need to be more open

AstraZeneca didn’t publicly reveal what caused the pause but did share this information with investors. This, says Duncan Matthews, was an example of an attempt to apply old methods of operating to a new situation.

Why we need to know what’s in placebos

A key part of clinical trials are placebos – alternative or inactive treatments that are given to participants for comparison. But a key problem, Jeremy Howick explains, is that some vaccine trials don’t reveal what their placebos contain. Without knowing what benchmark is being used, it’s then difficult for outsiders to understand the relative effect (and side effects) the vaccine has.

How will the vaccine be made and rolled out?

Preparing enough for the whole world

Universal demand for a COVID-19 vaccine means production bottlenecks are a risk. For the Oxford vaccine, production involves growing key components in human embryonic kidney cells, before creating the actual vaccine and then purifying and then concentrating it. Running this process at industrial scale, say Qasim Rafiq and Martina Micheletti, is one of the biggest challenges AstraZeneca faces.
A woman working in a vaccine manufacturing plant.
AstraZeneca and its partners are aiming to manufacture 2 billion doses of its vaccine by the end of 2021. RGtimeline/Shutterstock

Tobacco – an unexpected ally?

Vaccines contain organic products, which traditionally have been grown using cell cultures in containers called bioreactors. Recently plants have been adapted to function as bioreactors too, which could help production be massively increased. Tobacco may be especially useful: it grows quickly, is farmed all over the world, is leafy and easily modifiable. The tech hasn’t been approved for mass producing medicines – but demand may change that.

Keeping vaccines cool will be crucial

Because COVID-19 vaccines will contain biological material, they’ll need to be kept cold right up until they’re delivered, explains Anna Nagurney. Fail to keep them cool and they’ll become ineffective. Refrigeration will therefore be a major challenge in any roll-out campaign; an estimated 25% of vaccines are spoiled by the time they reach their destination. A potential solution could be to encase their heat-sensitive parts in silica.
A man in a lab coat stands in front of a freezer filled with medical supplies.
Cold storage facilities will be needed to store vaccines, while refrigerated trucks and planes will be needed to move them. Tony Karumba/AFP via Getty Images

‘Vaccine nationalism’ threatens universal access

Some governments are signing agreements with manufacturers to supply them with vaccines ahead of other countries. Poorer nations risk being left empty handed – putting people at risk and preventing any attempt to coordinate suppressing the coronavirus worldwide. It’s also unclear how access is being priced in these deals.

How to counter vaccine nationalism

India can play a key role in avoiding this “richest-takes-all” scenario, says Rory Horner. It’s traditionally been a major supplier of medicines to the global south, and has the capacity to create more vaccines for COVID-19 than any other country in the world. India’s Serum Institute has signed up to make 400 million doses of the Oxford vaccine this year, but with a population of 1.35 billion, how many will go abroad isn’t yet clear.
Mumbai medical worker prepares a vaccine
India’s track record in producing vaccines and key medical ingredients has led to it being labelled the ‘pharmacy of the world’. Shutterstock/ManoejPaateel

Who will get the coronavirus vaccine first?

We need to plan now, say Laurence Roope and Philip Clarke. Governments have big decisions to make. The pandemic is akin to a war situation, so there’s an argument these vital goods should be rationed and banned from private sale. Authorities also need to decide who should be prioritised: those most vulnerable, people most likely to spread the virus, or those who can kickstart the economy by returning to work.

How do you counter resistance and scepticism?

Public resistance is a sizeable problem – but nothing new

Surveys show that one in four New Zealanders remain hesitant about a coronavirus vaccine, while one in six British people would refuse one. But vaccine hesitancy has been around for a long time, writes Sally Frampton. And Steven King argues the past – such as when smallpox vaccines were resisted – may provide some solutions to this problem.

Are anti-vaxxers a problem?

Not all hesitancy is the same, says Annamaria Carusi. As well as the hardcore anti-vaxxers, plenty may resist COVID-19 vaccines on safety or animal welfare grounds. Indeed, while anti-vaxxers attract a lot of attention, their influence on vaccination rates is often overstated, argues Samantha Vanderslott. In fact, desire for a vaccine is so widespread and strong that anti-vaxxer positions may be harder to defend right now.

The far right is exploiting the pandemic

A recent report from the United Nations Security Council warned that extreme right-wing groups in the US are using the pandemic to “radicalise, recruit, and inspire plots and attacks”. Blyth Crawford gives a run-down of the major groups at work in America – what their aims are, the methods they’re using to reach people, and the key pieces of misinformation that they’re peddling.

How to build trust in vaccines

The usual strategy is to double down on positive messaging. But a better strategy, Mark Honigsbaum argues, would be to acknowledge that there’s a lot we don’t know about how some vaccines work, but that the benefits of taking vaccines far outweigh the risks. A further step could be to make sure that manufacturers are liable should vaccine recipients suffer negative effects. Often manufacturers are exempt.

Looking ahead

The future is full of possibility. COVID-19, Sars, Mers and the common cold are all caused by coronaviruses, and scientists are considering whether it’s possible to create a vaccine that could offer protection against them all – and perhaps even against an as yet unknown coronavirus we’re yet to encounter. Admittedly, having a vaccine that can do this seems unlikely in the near future. We shouldn’t get ahead of ourselves, though, says Sarah Pitt. No vaccine has yet completed its safety trials, and we can’t yet be sure that any vaccine will permanently prevent people from catching COVID-19. We need to prepare ourselves for the very real possibility that a COVID-19 vaccine only reduces the severity of symptoms or provides temporary protection.

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This course asks, ‘What is mindfulness?’ – but don’t expect a clear-cut answer

Mindfulness is everywhere in pop culture today, but that doesn’t mean people agree on what it means.

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54 mins ago

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March 23, 2023

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Practicing mindfulness doesn't have to mean being removed from the world. PeopleImages/iStock via Getty Images Plus
Text saying: Uncommon Courses, from The Conversation

Uncommon Courses is an occasional series from The Conversation U.S. highlighting unconventional approaches to teaching.

Title of course:

“What is Mindfulness?”

What prompted the idea for the course?

As a professor of religion and ethics, particularly Asian traditions, I had already been interested in teaching a course about mindfulness. Its popularity seems to be surging: I see “Mindful” on magazine racks, and almost everyone I’ve met at my university has used the word at some point.

But oftentimes people say to be “mindful” when they mean “pay attention” or “don’t forget”: being “mindful” of a slippery road, say, or telling students to be “mindful of the deadline.” I started wondering what other people meant each time they used the word. This made me realize my course shouldn’t be a lecture about mindfulness, but an opportunity to explore what it is in the first place.

What does the course explore?

The course explores the origins of mindfulness in yoga and Buddhism. Mindful meditation – being attentive to one’s body, feelings and thoughts – is part of one of the Buddha’s central teachings, the Noble Eightfold Path, and considered key to enlightenment.

But we explore the many meanings of “mindfulness” that have emerged in recent decades, too. American professor Jon Kabat-Zinn is credited with popularizing the kind of mindfulness that has caught on with non-Buddhists today, starting with his “mindfulness-based stress reduction” program in the 1970s.

Some people are upset that mindfulness has become too mainstream and fear that it has lost its intended meaning. Buddhism scholar Ronald Purser’s book “McMindfulness,” for example, argues that capitalist societies have embraced mindfulness as a way to put the burden of mental health back on the individual rather than address root problems.

Students in my class read a variety of these perspectives and discuss themes such as mindfulness and mental health, mindful eating and breathing, environmental mindfulness and even meditation apps. In the end, I want each student to decide for themselves what mindfulness is.

A woman in exercise clothes does a yoga pose inside a dark cathedral with stained glass windows.
Mia Michelson-Bartlett, yoga teacher and manager of visitors’ services, practices yoga and mindfulness meditation inside the Cathedral of St. John the Divine in New York City. Angela Weiss/AFP via Getty Images

Why is this course relevant now?

I first proposed this course right before the arrival of COVID-19, so when it launched for the first time, we met remotely over Zoom. I was tempted to drop the class after we went remote, but I quickly realized that it might help students who were wrestling with mental health issues at the beginning of the pandemic.

Each student kept a journal of our topics every week to practice mindfulness and to explore some of the therapeutic techniques. First, I asked them to find examples of the word in their everyday experiences – used on a poster at the student rec center, for example.

Later, I asked them to practice breathing and visualization techniques from the influential Vietnamese monk Thich Nhat Hanh, such as asking yourself every hour “What am I doing?” and reflecting on your mind, emotions and posture.

What’s a critical lesson from the course?

Buddhism changes dramatically depending on “whose” Buddhism you are talking about. The dalai lama’s form of Tibetan Buddhism, for example, is not the same as the Zen Buddhism of Thich Nhat Hanh.

A row of monks stand next to a small crowd of schoolchildren in uniform as one monk takes a child's hand.
Zen master Thich Nhat Hanh reaches for a student’s hand during a meditation walk on a ‘day of mindfulness’ in Hong Kong in 2007. Steve Cray/South China Morning Post via Getty Images

It’s the same with mindfulness. Thirteenth-century Zen master Dōgen taught pupils to seek mindfulness in seated meditation. Five hundred years later, on the other hand, Zen master Hakuin taught mindfulness in the midst of activity – practicing it not just on the meditation pillow, but amid the hustle and bustle of the streets.

All forms of Buddhism, though, focus on transforming suffering into lovingkindness. So teaching this course has persuaded me that if the way you teach mindfulness helps someone, it doesn’t matter if it’s “real” Buddhist mindfulness or not. If pop culture’s version of the concept relieves someone’s suffering, then I don’t want to be a gatekeeper and say, “This is not real mindfulness.”

What will the course prepare students to do?

All of the students in this course are first-semester freshmen. The class began as a way to get them to think critically about what mindfulness is but also offers tools to deal with the stress of college life.

Muscles grow after they heal and rest. The same is true when it comes to learning. Our minds need to take time to breathe, reflect on new information and absorb it.

I also hope students will understand that taking care of oneself can be an act of care for others. Just as on an airplane we are told to put on our own oxygen mask before helping the person next to us, we all need to take care of our own mental health in order to help those around us.

Kevin C. Taylor does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Post-bariatric surgery exercise modulates brain regions associated with regulation of food intake

Physical exercise practiced by patients submitted to bariatric surgery acts on brain regions involved in food intake, reducing hunger or accelerating satiety,…

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March 23, 2023

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Physical exercise practiced by patients submitted to bariatric surgery acts on brain regions involved in food intake, reducing hunger or accelerating satiety, for example. This was the result observed in a clinical trial conducted at Hospital das Clínicas (HC), the hospital complex run by the University of São Paulo’s Medical School (FM-USP) in Brazil. An article on the study, pointing to positive effects of exercise on obesity-related conditions in post-bariatric patients, is published in the International Journal of Obesity.

Credit: Carlos Merege Filho

Physical exercise practiced by patients submitted to bariatric surgery acts on brain regions involved in food intake, reducing hunger or accelerating satiety, for example. This was the result observed in a clinical trial conducted at Hospital das Clínicas (HC), the hospital complex run by the University of São Paulo’s Medical School (FM-USP) in Brazil. An article on the study, pointing to positive effects of exercise on obesity-related conditions in post-bariatric patients, is published in the International Journal of Obesity.

The study showed that an exercise training program starting three months after bariatric surgery produced functional alterations in brain networks associated with food intake and modified by obesity. The findings confirm the hypothesis that exercise and bariatric surgery act synergistically on the connectivity among brain regions associated with cognition, reward and emotional regulation, potentially moderating hunger and enhancing satiety.

According to the article, exercise increased the connectivity between the hypothalamus (the brain region that controls homeostasis, including regulation of appetite and energy expenditure) and the brain’s sensory areas. At the same time, it apparently decreased the link between the default mode network, which is more active during a resting state, and the salience network, the brain region involved in decision-making.

The researchers also found that exercise after bariatric surgery appeared to modulate the medial hypothalamic nucleus involved in appetite suppression and increased energy expenditure.

“The regulation of energy expenditure is governed by multiple internal and external signals. People with obesity display major dysregulation of brain regions associated with appetite and satiety. Our study showed that exercise by post-bariatric patients helped ‘normalize’ these complex networks so as to improve the central control of food intake. For example, some of these regions are activated and connect more intensely in people with obesity when they eat fatty or sugary food, increasing their desire to consume such food. We found that exercise counteracts this effect, at least in part,” Bruno Gualano, last author of the article, told Agência FAPESP. Gualano is a professor at FM-USP.

The study was supported by FAPESP via a research grant for the project “Effects of exercise training in patients undergoing bariatric surgery: a randomized clinical trial” and was part of the PhD research of Carlos Merege Filho, first author of the article, with a scholarship from FAPESP. The co-authors included Hamilton Roschel, Marco Aurélio Santo, Sônia Brucki, Claudia da Costa Leite, Maria Concepción García Otaduy and Mariana Nucci (all of whom are affiliated with HC-FM-USP); and John Kirwan of Pennington Biomedical Center (USA).

Considered one of the world’s main public health problems, obesity is a chronic disease characterized by excessive body fat accumulation and a major risk factor for cardiovascular and musculoskeletal disorders, as well as severe COVID-19. The parameter used for diagnosis in adults is body mass index (BMI), defined as weight in kilograms divided by height squared in meters. A BMI between 25 and 29.9 indicates overweight, while 30 or more signals obesity, according to the World Health Organization (WHO).

Brazil has one of the highest rates of overweight and obesity in the world. According to projections, almost 30% of the adult population will be obese in 2030. A billion people, or 17.5% of the world’s adult population, will be obese by then, according to the World Obesity Atlas 2022 published by the World Obesity Federation.

Importance

From the clinical standpoint, Gualano believes, the findings suggest that exercise should be considered an important complementary therapy to improve brain functions and enhance the known benefits of bariatric surgery, such as a reduction in cardiometabolic risk factors, as well as preservation of muscle mass and bone health.

He and his group have been conducting research in this field since 2018, as evidenced by other publications, one of which showed that exercise attenuated and reversed loss of muscle mass, improving muscle strength and function in post-bariatric patients. Genotypic and phenotypic analysis evidenced metabolic and structural remodeling of skeletal muscle.

In another study, exercise reduced risk factors for diseases associated with obesity, such as diabetes, high blood pressure and atherosclerosis (hardening of the arteries), by increasing sensitivity to insulin, combating inflammation and improving the health of blood vessels.

Methods

The randomized clinical trial reported in the International Journal of Obesity involved 30 women aged between 18 and 60 who had been submitted at HC-FM-USP’s bariatric surgery unit to a Roux-en-Y gastric bypass, which creates a small stomach pouch to restrict food intake and bypasses a large portion of the small intestine to limit calorie absorption. A majority of patients admitted to the unit are women. 

Half the study sample were randomly assigned to a six-month exercise program of resistance and aerobic training three times a week, starting three months after the operation and supervised by a team of physical education professionals.

Clinical, laboratory and brain functional connectivity parameters were assessed at the start of the trial, as a baseline, and again three and nine months after the operation. Functional magnetic resonance imaging (fMRI) was used to detect connectivity between anatomically distinct brain areas organized as networks, and to analyze the combined effects of the surgical procedure and exercise training. Data collection began in June 2018 and ended in August 2021.

“The literature has already shown that post-bariatric patients have many brain alterations compatible with improved control of appetite, satiety and hunger in neural circuits that govern food intake. Our study found that exercise training bolstered this response,” Gualano said, noting the importance of lifestyle changes to maintain the benefits of weight loss for people with obesity.

Bariatric surgery can currently be performed on patients with a BMI of between 30 and 35 and type 2 diabetes that has not been controlled for more than two years, and patients with a BMI over 35 who have other diseases associated with overweight, such as high blood pressure, sleep apnea or hepatic steatosis (fatty liver disease). For people with comorbidities, the recommended BMI is over 40.

In the past five years, 311,850 bariatric surgeries have been performed in Brazil; 14.1% were paid for by the SUS (Sistema Único de Saúde), the national health service. The rest were covered by insurance policies or paid for privately, according to the Brazilian Bariatric and Metabolic Surgery Society (SBCBM).

“Regular exercise is known to induce several physiological adaptations that translate into health benefits. These benefits are reversed if the patient stops exercising regularly. Our study didn’t measure the duration of the brain changes induced by exercise, however. They’re highly likely to diminish and possibly even go into reverse as the amount and intensity of exercise decrease. It’s crucial to adopt a healthy lifestyle in order for the responses to bariatric surgery to be long-lasting,” Gualano said.

Next steps for the research group will include studying the effects in people with obesity of exercise and diet combined with other weight loss strategies, including new drugs such as peptide analogs or incretin mimetics, a class of medications commonly used to treat type 2 diabetes. Incretins are gut hormones that aid digestion and blood sugar control by signaling to the brain to stop eating after a meal.

In early January, the National Health Surveillance Agency (ANVISA) approved semaglutide as an anti-obesity drug for long-term weight management. The drug had previously been approved only for patients with type 2 diabetes. It is the first injectable anti-obesity medication available in Brazil and is supposed to be administered once a week. It is said to enhance satiety, modulate appetite and control blood sugar. 

About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe

Journal

International Journal of Obesity

DOI

10.1038/s41366-022-01251-8

Article Title

Exercise modifies hypothalamic connectivity and brain functional networks in women after bariatric surgery: a randomized clinical trial

Article Publication Date

30-Dec-2022

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The CeMM & Angelini Ventures Healthy Lifespan Expansion Initiative

CeMM and Angelini Ventures are joining forces to support CeMM Principal Investigators Laura de Rooij and André Rendeiro in critical lifespan expansion…

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March 23, 2023

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CeMM and Angelini Ventures are joining forces to support CeMM Principal Investigators Laura de Rooij and André Rendeiro in critical lifespan expansion initiatives leveraging a novel academic/entrepreneurial dual-track program. De Rooij and Rendeiro, in collaboration with their teams, will lead an original research program on healthy lifespan expansion.  In parallel, they will collaborate on venture creation based on scientific and business insights developed by their work. Venture creation and related business development activities will take place along with scientific research.  The expectation is that this double-track initiative will allow for virtuous feedback cycles, propelling innovation through scientific research and bold venture creation goals.

Credit: CeMM

CeMM and Angelini Ventures are joining forces to support CeMM Principal Investigators Laura de Rooij and André Rendeiro in critical lifespan expansion initiatives leveraging a novel academic/entrepreneurial dual-track program. De Rooij and Rendeiro, in collaboration with their teams, will lead an original research program on healthy lifespan expansion.  In parallel, they will collaborate on venture creation based on scientific and business insights developed by their work. Venture creation and related business development activities will take place along with scientific research.  The expectation is that this double-track initiative will allow for virtuous feedback cycles, propelling innovation through scientific research and bold venture creation goals.

(Vienna, 22 March 2023) Some societal challenges are of such importance to assume the central stage in the public discourse on sustainability and the future of humanity. Such a challenge is aging. Aging is a multidimensional phenomenon, occurring at the individual and population levels of society and on the molecular, cellular, and organ level of the human body. The urgency of dealing with the consequences of aging is illustrated by the fact that in just over ten years from now, more than a third of the population of Italy, one of the world’s most rapidly aging countries, will be over 65 years of age. Expanding the lifespan in which individuals enjoy a healthy status, in which they can be independent and productive, is critical for economic, social, and cultural reasons.

The fundamental mechanisms of aging, at the molecular, cellular, and tissue level, are still unclear and most single theories fail to explain the phenomenon. Scientific leaders are increasingly interested in combining cutting-edge research with immediate value creation and effective societal impact. Laura de Rooij and André Rendeiro will be supported by a network of mentors and experts. At CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, the team will benefit from access to faculty peers, the center’s scientific leadership, a scientific advisory board, and the biotech ventures built in CeMM’s ecosystem of spinoffs. Through Angelini Ventures, the team will be supported to ideate and develop viable start-up companies emerging from their work and have access to an international network of investors, healthcare experts, and industry innovators.

 

“The Angelini Ventures team is delighted to partner with CeMM to collaborate on accelerating lifespan expansion research and venture creation. We believe this type of collaboration is the connective tissue between innovation and entrepreneurship. By combining our venture creation capabilities with the breakthrough research from CEMM, we can accelerate the pace of healthcare transformation,” says Paolo Di Giorgio, Chief Executive Officer of Angelini Ventures.

“CeMM is proud to pioneer a new training, research, and innovation method meant to foster a novel generation of professionals familiar with both the research and business worlds. In addition to expecting commercial success, the desired outcome is to create leaders able to inspire a new generation of scientists. Our goal is for the dual track of scientific research and business development to expand beyond the CeMM-Angelini network,” says CeMM Scientific Director Giulio Superti-Furga.

 

About the Principal Investigators

Laura de Rooij joined CeMM as principal investigator in September 2022. Her lab focuses on deciphering the transcriptomic landscape and role of circulating endothelial cells in health and aging. Laura de Rooij studied Biomedical Sciences at the University of Amsterdam (The Netherlands). She then joined the Stem Cell and Cancer Research Institute at McMaster University in Hamilton (Canada), where she studied the role of RNA binding proteins in leukemic stem cells via an in vivo two-step CRISPR-Cas9-mediated screening approach. For her post-doctoral studies, she returned to Europe to work under the mentorship of Prof. Carmeliet in the lab of Angiogenesis and Vascular Metabolism at VIB-KU Leuven (Belgium). Here she led and contributed to numerous single-cell transcriptome atlases of endothelial cells, generated from a diverse range of tissues, preclinical models, and clinical patient material in health and disease. Her studies have shed new light on the degree of vessel subtype heterogeneity in different tissues, as well as the altered composition and rewired molecular circuitries of endothelial cell subtypes in disease. Moreover, her efforts led to the discovery of previously unknown vascular subtypes and functions, including endothelial cells with a lipid-processing phenotype and potential prognostic relevance in breast cancer, and endothelial cells with a putative pro-fibrotic function in COVID-19. At CeMM, her lab focuses on deciphering the transcriptomic landscape and role of circulating endothelial cells in health and aging.
Read more about Laura de Rooij’s research

André Rendeiro is a Principal Investigator at CeMM since June 2022. He leads a group studying how cells interact to generate complex physiology in the human body, and how this changes over the lifespan of individuals and gives rise to disease. To do that, his group develops computational methods for the analysis of spatial data (spatial transcriptomics, highly multiplexed imaging, histopathological images), and its integration with various modalities of molecular, demographic, and clinical data of individuals along their lifespan. Prior to starting his group, André studied in Portugal, Austria, and Norway and earned his PhD in Molecular Medicine at CeMM in Vienna. During his PhD he developed methods for high-throughput cellular profiling and perturbation at single-cell resolution, applying them to leukemia, in the lab of Christoph Bock at CeMM. Between 2020 and 2022 he was a Postdoctoral Associate at the Institute for Precision Medicine and the Institute for Computational Biomedicine at Weill Cornell Medicine in New York. There he developed computational methods for the analysis of highly-multiplexed imaging that incorporate expression, morphology, micro-anatomy, and clinical covariates, in the lab of Olivier Elemento. He led the first tissue-level, single-cell resolution maps of lung pathology during COVID-19, and also contributed to the study of cancer, lung development, and disease, as well as COVID-19 immunology.
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The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences is an international, independent, and interdisciplinary research institution for molecular medicine under the scientific direction of Giulio Superti-Furga. CeMM is oriented toward medical needs and integrates basic research and clinical expertise to develop innovative diagnostic and therapeutic approaches for precision medicine. Research focuses on cancer, inflammation, metabolic and immune disorders, and rare diseases. The Institute’s research building is located on the campus of the Medical University and the Vienna General Hospital. www.cemm.at

Angelini Ventures, the venture capital arm of Angelini Industries, is an early-stage investment firm focused on accelerating disruptive innovations and trends in digital health and life sciences. The group will invest €300M across a global portfolio led by investment professionals and advisors in Europe, North America, and Asia. Angelini Ventures has deep domain expertise and leverages a global team, advisors, and strategic partners to help entrepreneurs scale their businesses into transformative category-leading companies. www.angeliniventures.com

Angelini Industries is a multinational industrial group originally founded in Ancona (Italy) in 1919 by Francesco Angelini. Today it is a solid, structured industrial business with around 5,800 employees operating in 21 countries.  Angelini Industries operates in the health, industrial technology, and consumer goods businesses. Its investment strategy aimed at growth, constant commitment to research and development, and deep knowledge of markets and business sectors make Angelini Industries an Italian leader in the industries in which it operates.  The group is committed to reducing its environmental impact and finding increasingly cutting-edge circular economy solutions. It adopts the most advanced health and safety standards for workers and the most rigorous processes to ensure the highest quality by verifying the entire supply chain: from supplier certification to the control of raw materials, the production process, the finished product, and packaging, to spot checks at the point of sale.  For over 100 years, the Angelini family has steered the development of Angelini Industries with an entrepreneurial style typical of Italian family businesses. www.angeliniindustries.com

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