How iGUARD disables viruses
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.
Prof. Dr. Dr. Axel Schambach wants to be prepared for the next pandemic. “Our goal is to be able to develop tailor-made therapies as quickly as possible.” Normally it takes several years or even decades to develop a new drug, which is eons for viruses. “We saw with SARS-Cov-2 how quickly a virus can mutate. First came the Alpha variant, then the Delta variant, then Omicron, and now we again have new variants, meaning the vaccination strategies, which were developed very quickly at the time, are not effective for these variants,” explains Schambach, Professor of Molecular Medicine and Gene Therapy at the Hannover Medical School. “But what we always know very early on—and this was also the case with the virus from Wuhan—is how the virus is genetically constructed.” Using AI technology, Schambach plans to match this information with other virus strains. “We are looking to see if there are any particular Achilles’ heels worth targeting that then make it difficult for the virus to mutate.”
Once the siRNA enters the host cell, the cell inspects the viral mRNA for a complementary segment. Once the genetic counterpart to the siRNA has been identified, mRNA and siRNA combine to form a double strand. “When this happens, it is called RNA interference,” Schambach explains.
The double strand is recognized by an enzyme, which is a component of Argonaute proteins, and cleaved into small pieces. The mRNA is normally tasked with transporting the virus’ genetic information for protein synthesis; however, the cut mRNA fragments can no longer be used as a template for protein production, severely disrupting the virus’ replication process to the point that it can no longer reproduce. “In this way, we are generating endogenous signals that help the body destroy the virus itself,” says Schambach.
“Simplicity is beautiful. According to this principle, basically, all we are doing is adding siRNA. The cell does the rest,” says Schambach, explaining the elegance of the methodology. “All we are doing is giving the initial push, like tipping over the first domino. This makes our delivery method extremely simple.”
The double strand is recognized by an enzyme, which is a component of Argonaute proteins, and cleaved into small pieces. The mRNA is normally tasked with transporting the virus’ genetic information for protein synthesis; however, the cut mRNA fragments can no longer be used as a template for protein production, severely disrupting the virus’ replication process to the point that it can no longer reproduce. “In this way, we are generating endogenous signals that help the body destroy the virus itself,” says Schambach.
“Simplicity is beautiful. According to this principle, basically, all we are doing is adding siRNA. The cell does the rest,” says Schambach, explaining the elegance of the methodology. “All we are doing is giving the initial push, like tipping over the first domino. This makes our delivery method extremely simple.”
Currently, Axel Schambach’s team is focusing on parainfluenza viruses. This is a family of viruses that can cause a mild cold and more severe respiratory illnesses, such as bronchitis and pneumonia, illnesses which can be life-threatening, especially in patients with compromised immune systems and transplants. Since there is no specific antiviral therapy, current treatment for parainfluenza infections only focuses on symptom relief.
That is about to change. “We basically looked at the whole genome with AI to see which areas of the viral mRNA are both particularly vulnerable and, at the same time, resistant to mutations,” Schambach explains. Small, complementary RNA snippets—so-called small interfering RNAs or siRNAs for short—then dock onto these selected regions. “In principle, the RNA snippets only need to be between 16 and 20 base pairs long,” says Schambach. “Since a virus genome is relatively large, we can attack it with the RNA snippets in several places.”
That is about to change. “We basically looked at the whole genome with AI to see which areas of the viral mRNA are both particularly vulnerable and, at the same time, resistant to mutations,” Schambach explains. Small, complementary RNA snippets—so-called small interfering RNAs or siRNAs for short—then dock onto these selected regions. “In principle, the RNA snippets only need to be between 16 and 20 base pairs long,” says Schambach. “Since a virus genome is relatively large, we can attack it with the RNA snippets in several places.”
The team is focusing on respiratory viruses and is working to develop an inhalable therapeutic agent. “This is particularly exciting because there are relatively few companies in the pharmaceutical industry working on this,” says Schambach. “We really broke new ground here, and in cell culture, we showed that it works. Not only in animal studies but also in living lung cells from patients.”
Therapeutics based on RNA interference (RNAi) represent a new class of drugs. The first RNAi therapeutic was approved for patient treatment in 2018. Currently, RNAi drugs are being examined in clinical trials for various indications. “RNAi is broadly applicable to all kinds of viral infections, especially those we are not even aware of yet,” says Schambach. “Also, there are just a lot of diseases where the issue is protein overexpression. This is another area we can target, reestablishing the proper protein levels in a self-regulating way.”
Therapeutics based on RNA interference (RNAi) represent a new class of drugs. The first RNAi therapeutic was approved for patient treatment in 2018. Currently, RNAi drugs are being examined in clinical trials for various indications. “RNAi is broadly applicable to all kinds of viral infections, especially those we are not even aware of yet,” says Schambach. “Also, there are just a lot of diseases where the issue is protein overexpression. This is another area we can target, reestablishing the proper protein levels in a self-regulating way.”
The major advantage of the technology is that suitable siRNAs can be found and synthesized very quickly thanks to the support of the AI algorithm and the preclinical development pipeline tailored to it. Axel Schambach, who worked in Central Africa for several years, believes it is important that new RNAi drugs are produced quickly and cost-effectively. “Every patient who needs the therapy should be able to benefit from it. And for me, that explicitly includes developing and emerging countries.”
Schambach is convinced of the success of his research, particularly because of his colleagues. “We have a whole team of people who are excited about new topics, who do not back down from challenges, and who do not give up at the first signs of a problem; people who are eager to innovate and push new things forward.” Supporting and encouraging young colleagues is also especially important for him. As he says, “It is vital for us to have young people on the team who can tackle such developments over the long term and commit to them for decades to come.” The iGUARD team around Axel Schambach, Philippe Vollmer Barbosa, Prof. Armin Braun, and Prof. Adrian Schwarzer also brings people with different core competencies together. To that effect, Schambach summarizes it well when he says, “Much of what we do is a synergistic team effort, working together to find the right solutions for tomorrow’s medicine.”
Schambach is convinced of the success of his research, particularly because of his colleagues. “We have a whole team of people who are excited about new topics, who do not back down from challenges, and who do not give up at the first signs of a problem; people who are eager to innovate and push new things forward.” Supporting and encouraging young colleagues is also especially important for him. As he says, “It is vital for us to have young people on the team who can tackle such developments over the long term and commit to them for decades to come.” The iGUARD team around Axel Schambach, Philippe Vollmer Barbosa, Prof. Armin Braun, and Prof. Adrian Schwarzer also brings people with different core competencies together. To that effect, Schambach summarizes it well when he says, “Much of what we do is a synergistic team effort, working together to find the right solutions for tomorrow’s medicine.”
“Every patient who needs the therapy should be able to benefit from it. And for me, that explicitly includes developing and emerging countries.”
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