MucBoost gives human mucus an evolutionary upgrade
Viruses are an unpredictable threat to global health, the economy and society - we have known this at least since the SARS-CoV-2 pandemic. Several million people have died since the beginning of the pandemic. There is still a lack of effective therapeutics against SARS-CoV-2 and emerging variants. The truth is: there are still no therapeutics against many other viruses either. Potentiating viral loads, high mutation rates and limited targets are inherent to viruses, making them true "survival artists" and placing high demands on drug development. The great desire to overcome the pandemic helped new technologies based on mRNA and equally new ways in drug delivery to achieve a rapid breakthrough in vaccine development – contrary to the expectations of many experts.
Similarly, breakthroughs in antiviral drug development are needed. Highly innovative approaches are required to combat viral infections. That is why SPRIND is supporting new technological approaches for breakthrough innovations to combat viral infections with this Challenge.
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Goal of this Challenge: New approaches for the development of antiviral therapeutics
The goal of the Challenge is to expand the repertoire of antiviral therapeutics with breakthrough technologies so that new treatment options will be available in the future and patients can be helped quickly. The Challenge teams are developing approaches for broad-spectrum antivirals and platform technologies for the rapid development of antiviral agents. At the end of the Challenge, the active agent resulting from the solution approach has to be tested in a proof of concept adapted to the development stage.
The Teams
CRISPR/CAS13
Team CRISPR antivirals use the antiviral defense system CRISPR/Cas13 - perfected by millions of years of evolution by bacteria - to block proliferation and cytopathic effects of RNA viruses such as SARS-CoV-2 through cleavage of their viral genome and mRNA.
iGUARD platform
The iGUARD team develops next-generation RNAi-based molecular therapeutics against respiratory viruses using machine-learning for automated target identification and an optimized vector platform for delivery and preclinical validation in human patient-relevant models.
Virustrap
Team Virustrap uses DNA Origami technology to build nano scale traps for viruses.
MucBoost
Team MucBoost develops an upgrade against pathogens: Boosting the antiviral efficacy of mucus.
Participating in the Challenge pushes the teams to their full potential. We therefore provide intensive and individual support. This includes funding the teams as well as individual support from a Challenge coach, who has significant experience in the Challenge area and has already implemented high-impact innovations.
In the first year of the Challenge, SPRIND funded the teams' work with up to 700,000 euros, in the second year with up to 1.5 million euros, and in the current third year with up to 2.5 million euros each. We provide funding quickly and unbureaucratically, so that the teams can concentrate fully on their innovations.
Thinking one step further: Ideas with the potential for disruptive innovations must be brought to market to benefit patients. That is why SPRIND continues to support projects with potential for breakthrough innovation even after the Challenge has ended.
In October 2023, the expert jury selected the participants for the third and final stage of the 'Broad-Spectrum Antivirals' challenge. Four teams will each receive up to 2.5 million euros over the next twelve months for the further development of their radically new of antiviral therapeutics.
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Science Youtuber Jacob Beautemps introduces the six Challenge teams of stage 2 at Breaking Lab
Revolution in medicine? Jacob Beautemps takes a closer look at CRISPR CAS technology
Our jury of scientists and science entrepreneurs will evaluate all applications and select the teams that have what it takes to implement breakthrough innovations.
Joachim Spatz
Karin Mölling
Detlev Riesner
Nikolaus Rajewsky
Manfred Schubert-Zsilavecz
Holger Reithinger
February 28, 2022
What is an "Innovation Challenge"? What role is played by competition and cooperation? And what are the current SPRIND challenges about? Our host Thomas Ramge asks: Dr. Diane Seimetz, co-founder of Biopharma Excellence and innovation coach, and Dr. Jano Costard, Challenge Officer of the Federal Agency for Disruptive Innovation.
Listen to the episode (in German).
Do you have further questions?
If you have any questions or suggestions, please feel free to contact us at challenge@sprind.org.
Mucus. Other people might find it disgusting at first, but Prof. Dr. Daniel Lauster is fascinated by it. Our body produces a good two liters of mucus every day. As the body’s first internal line of defense, it is constantly intercepting pathogens for us. But some viruses are not stopped by the mucus barrier, and they infect us. Daniel Lauster, biophysicist and director of the MucBoost team, wants to change that—by strengthening the natural protective function of mucus.
“If we fill the weak spots in mucus with virus-binding protein molecules, we can give mucus an evolutionary upgrade,” says Lauster. Protein molecules can be thought of as small connecting elements. They anchor themselves in the mucus with one end and dock onto the virus with the other. If this happens successfully, the virus gets transported with the mucus via the movement of the cilia on the mucosa to the pharynx and from there, to the stomach, where it is destroyed by stomach acid.
“If we fill the weak spots in mucus with virus-binding protein molecules, we can give mucus an evolutionary upgrade,” says Lauster. Protein molecules can be thought of as small connecting elements. They anchor themselves in the mucus with one end and dock onto the virus with the other. If this happens successfully, the virus gets transported with the mucus via the movement of the cilia on the mucosa to the pharynx and from there, to the stomach, where it is destroyed by stomach acid.
The modular concept makes it possible to react very specifically to a new virus. However, the MucBoost nasal spray can also be used as a broad-spectrum therapeutic agent. “For us, conserved regions are particularly interesting. These are regions that, despite virus evolution, have remained unchanged. It is well conserved because viruses always have to bind to sialic acid to get into the cell. As a result, our influenza binder attaches close to the sialic acid binding site,” Lauster explains. Initial laboratory tests show that the concept is working. “We can bind to several strains of the seasonal flu virus H3N2, as well as to H1N1, and the avian flu strain H7N1.”
When Daniel Lauster started SPRIND’s Broad-Spectrum Antivirals Challenge, the corona pandemic was in full swing. At the time, the MucBoost team initially focused on developing a nasal spray against SARS-CoV-2, and since then, the team has switched to fighting influenza viruses. But in principle, the MucBoost concept can be applied to many virus types, even those still unknown.
That is because as soon as the viral surface proteins, also known as spike proteins, can be biotechnologically produced, the scientists can start looking for a suitable viral adapter. “We put different peptide variants on the surface of a virus protein and look at what it, or its spike, binds to best,” says Lauster. He identifies the binders at the molecular level, explaining, “I am a big fan of designing antiviral molecules using biophysical methods because you can visualize what is really happening at a very high resolution.”
That is because as soon as the viral surface proteins, also known as spike proteins, can be biotechnologically produced, the scientists can start looking for a suitable viral adapter. “We put different peptide variants on the surface of a virus protein and look at what it, or its spike, binds to best,” says Lauster. He identifies the binders at the molecular level, explaining, “I am a big fan of designing antiviral molecules using biophysical methods because you can visualize what is really happening at a very high resolution.”
While other scientists are engaged in basic research, Daniel Lauster is attracted by something else. “I do not want to create exotic structures that can potentially only be published in a paper. I want to develop something that can be used practically, something that is useful for people.”
The nasal spray, which will soon undergo initial animal studies, could be used directly in two different ways: Because it reduces the concentration of the virus, it could weaken the course of the disease in newly ill patients while also being used preventively. “I see it as a supplement to a mask,” says Lauster. “That is why we call it the invisible mask, because there are situations where you cannot wear one, like when eating and drinking.” In this way, disease-causing viruses would be directly filtered out by MucBoost upon contact with the mucus, preventing infection.
The nasal spray, which will soon undergo initial animal studies, could be used directly in two different ways: Because it reduces the concentration of the virus, it could weaken the course of the disease in newly ill patients while also being used preventively. “I see it as a supplement to a mask,” says Lauster. “That is why we call it the invisible mask, because there are situations where you cannot wear one, like when eating and drinking.” In this way, disease-causing viruses would be directly filtered out by MucBoost upon contact with the mucus, preventing infection.
Daniel Lauster has devoted himself entirely to the subject of slime. While MucBoost is about increasing the effectiveness of mucus, in another research project (MucPep) he is looking for ways to reduce mucus, like in cystic fibrosis, a disease which is incurable to date. But it is not just mucus in the lungs that interests him. “The surface area of mucus in our body covers around 200 square meters, but its composition varies depending on the tissue.” MucBoost could quite possibly also be used in other regions of the body in the future, like in our intestines. “We can adjust our slime binder accordingly. It is stable at body temperatures and can survive passing through the stomach.” Therefore, it would be possible to create oral therapy for intestinal viruses or bacterial toxins.
“I do not want to create exotic structures that can potentially only be published in a paper. I want to develop something that can be used practically, something that is useful for people.”
There is no danger of Daniel Lauster getting bored. The 38-year-old has not only been a junior professor for biopharmaceuticals at the Institute of Pharmacy at the Freie Universität Berlin since May 2023, he is also still studying there at the same time. Alongside his doctoral thesis in Experimental Biophysics, he recently began studying medicine. “If you are really dedicated to science, you have to be fully committed. You have to be intrinsically motivated, otherwise it is not going to work out,” says Lauster. “But it is great when ideas work. Translational research is exciting to me because I believe I will be able to experience the success of my research myself while also making a positive contribution to society.”
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