The Life Science Open Space is an event for scientists, innovators, entrepreneurs, doctors, brokers, investors, and officials – who share a commitment and drive for cooperation in solving problems, facing challenges, and developing INNOVATIONS FOR THE HEALTH AND QUALITY OF LIFE.
🔸 Hans Hofstraat – RNA revolution – Insights about the pharmaceutic potential of RNA and why it got the Nobel Prize this year.
Ingmar Hoerr was chairman of the Board of directors „Aufsichtsrat“ of CureVac AG and he served as founding CEO for 18 years. In 2000 he founded “CureVac, the RNA people“ together with colleagues in Tübingen, Germany. His entrepreneurship was motivated by his surprising discovery during his doctoral research that naked mRNA is capable to be expressed in vivo without the risk of rapid degradation and the ability of generating strong specific immune responses, in contrary to what had previously been believed. From this key discovery, Ingmar Hoerr, Steve Pascolo and Florian von der Mülbe built up a company that is now the most advanced company in the research and development of mRNA-based drugs. mRNA-based drugs can be developed for a huge variety of diseases and infections.
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Uh anyhow it’s really nice to be in grco again uh it was the ’90s um when I was a young boy after school I went by bicycle to kco and it was really really uh a nice uh thing um and uh yeah I love Poland somehow uh I always come back to
Poland because of these times extraordinary times thank you very much so let’s start um on the RNA Revolution it going forward okay it’s going forward yeah you know the Nobel Prize given this year to katalin kico Drew vicman one entrepreneurs working on the RNA subject and actually their technology saved the
World because uh it was the the principle of the corona vaccines uh their technology uh the RNA modifications they did well RNA let’s come um to RNA itself um it’s a really really nice interesting molecule a lot of people forgot about it um especially in the ’90s nobody was working on RNA
But it’s the oldest molecule in the world the first molecule first biomolecule was RNA indeed that’s really interesting why nature was developing this kind of molecule um and you know if you work with RNA it seems RNA is very unstable when I was in my lab uh doing the
PHD it was a hassle to work with RNA and scientists they believe RNA is very unstable you have to avoid it to work with RNA why is like that because I’m coming from a chemistry department so therefore chemically RNA is very stable it’s a more stable molecule
Actually uh more stable than proteins or than even DNA you can boil RNA you can heat it up 100° um and nothing happens to RNA so therefore chemically it’s really stable and that’s the reason why nature developed molecules destroying RNA called rnases destroying enzymes of uh
RNA and rnas are all around you know if you speak um there are rnases um and rnas destroy the RNA and that’s the artifact seeing in the lab if you work with RNA a lot of RNA is around therefore RNA is going to be really uh easily
Destroyed and therefore you know this is the kind of the the thing you have to think about it’s the oldest molecule in the world the most stable molecule we have in Biochemistry so this was the beginning of the uion in the world RNA was there
DNA you can see the double uh strand DNA we know the DNA it’s our chromosomes chromosome material um and people used to work with DNA for a lot of times um you know gene therapy for example in ’90s um and were a lot of problems using the gene therapy approach because DNA is
Very stable it has to be inherited from generation to generation therefore it’s a stable molecule um and there are not that many DN so destroying enzymes of DNA then RNA is destroying enzymes of RNA so therefore people working with DNA a long time um but DNA uh it’s very hard
To control once DNA is in your body it’s expressed so proteins are made for kind of weeks you don’t know how long exactly proteins are made from that using RNA it’s more easy because RNA is destroyed in a couple of hours or days as you want you have a mechanism to stabilize RNA
Therefore you get one shot RNA you know for two days there’s an expression that the RNA is gone that’s not the case as DNA you never know what happens to the DNA injected into your body so again RNA is heat stable it’s well soluble soluble and uh you can easily produce large
Quantities of RNA that’s also possible so actually I’m from tuban that’s the sou part of Germany um and actually um RNA was discovered and DNA as well in tubing and by F meure at that time uh in in the 80s and the 1800s um he didn’t
Really know what he detected uh so it was long before uh the code uh the genetic code and uh the things like that uh he was just thinking is something is not a protein but it’s in every animal I find it so it must be very important that was his measures at that
Time and um it’s interesting that in tuban the RNA Revolution was started uh by our company so we got entrepreneurs and interestingly it entrepreneurs like the hop the sap founder or Bill Gates uh Microsoft because somehow it seems RNA is a kind of it molecule it’s information molecule it’s called
Messenger RNA messenger gives you information to the cells and that’s interesting long before AI think um it was already clear to me that’s quite easy to speak with the body to talk the body what to do if there’s a health issue in the body so that’s tubing and you can see
It’s a very nice medieval town uh and on the left side there a new technology park like here um 20 years ago and also there were a lot of Publications on this technology and this were actually our first Labs at the University where we can use could use old chemistry faculty
Labs where we started the business due to a grant to our um B wenberg so the state of B wenberg gave us some some money to start the business otherwise it would have been very um tough actually we were quite young guys from the studies you know and going to the VC
Companies they say well who are you why you think you want you want to roliz revolutionize the world how you dare to do that so therefore it was qu quite impossible to get money funding so this kind of uh situation at the University um our first employee um in our
Lab and our conference room in front of the elevator so it was always blink blink blink when we were talking people were coming coming out and in yeah and then we moved in 2003 to the technology park in tuban uh we were the first ones in the technology park
Because it was a very dark time uh a lot of uh companies went insolvent um so we already only left and our our company car uh as well we’re very proud guess we are Germans we are proud on cars so therefore our first company cars so therefore cuc developed quite nicely and
It’s also noted in NASDAQ um uh in New York um yeah and then we got our first money from a small Venture company in 2003 our employees then 2090s ’90s now they’re double or triple of four time five time size like this many more people are engaged here um and uh of
Course we are very proud that we have a lot of collaborations uh with a lot of companies also Vis M The Gates Foundation so that’s quite interesting and it’s a really neat that we also get uh knowhow from other parts of the science scientific Community
Well I already told you um I think the most important thing for us was that we in uh implemented the pharmaceutical um production so the GMP production good manufacturing practice uh production that’s not easy because you have to maintain all the things like the farma industry like The Big farma Industry and
We were quite small company not knowing exactly what to do and as think this was a really really really really strong impact also for the others following us therefore um we invest a lot of money to get this approval and to start clinical trials because without clinical trials
Just having mice data it tells nothing so people really want to see clinical trial data on humans so this was the most important impact uh in our development that we could start clinical trials with humans so we did a lot of Trials um already um in flu um in polio
Uh and of course covid as well um and let’s come again to AI things it’s about information so it’s an information driven Pharmacy um um pharmaceutical it’s from nature because we don’t modify RNA uh now we have seen that it’s needed to modify the RNA like bch and Monna
Pudo seal is a new building block uh artificial builing Block in RNA but anyhow um it’s kind of a software approach do that and once again from school you maybe know uh DNA chromosome material then there’s the messenger the RNA and from this messenger proteins are
Made and that’s some a lot of important patterns uh there’s also kind of uh struggles with the others uh B and Monna about patterns we uh sub submitted already in the beginning of the 2000s a very important um and you can s see the infringement um uh uh uh uh uh
Battle with um biontech it’s on this patent it’s a patent called GC enrichment GC means guanosine cin they are two building blocks of the RNA you can see these are the adanin tumin guanin cin building blocks U adinin and tumin are binding with two hydrogen bonds and guanin cin with three hydrogen
Bonds so that means the more hydrogen bounds the more stable the RNA is and that’s the patent uh we found out that we should use GC guanosine and cine um the more we have of this basis the more stable the RNA is and that’s a patent where’s the conflict about and you can
See that’s the kind of AI language of the genetic code um triplet is coding for one amino acid amino acids uh getting a protein um and you can just use this scheme to do any protein you want uh you can code anything what you really want on RNA so it’s an algorithm
You you can use what we implemented were some called of untranslated regions so Regions they’re just uh for stabilization of the RNA on five Prime on the one hand and three Prime on the other hand that the RNA is kind of complexed and stabilized uh with proteins uh which are uh
Available in the cell so this a kind of natural stabilization process we don’t use any modified uh bases like uh Mna and btech and this is the technology of kiaro the Nobel Prize winner she was just replacing urasil that’s a building block of RNA with pseudo rasil it’s a small
Difference you can see here uh there’s one more n um included in that or the N is Switched uh from one place to the other place um and uh this actually is an interesting technology because it uses the immune response so we were aware about it already U 15 years back
When she was was applying uh also in qac uh we should use her patent and we should use her technology and she was using that because the immon response was somehow declining so when you inject RNA in the body RNA is a danger signal so if there’s RNA in the body appearing
Body gets into danger so you get a huge dangerous signals uh huge immune response and the reason why it’s like that because body is fearing there’s a virus attacking it there are lot of RNA viruses around therefore RNA gives you a danger signal in the body so if there’s
Somebody some some RNA attending the body outside of any cells body gets in danger and what kico did uh the pseudo Ral is somehow de missing the danger signal so the danger signal is reduced and that was the reason why cuck failed um in the covid vaccines because cuck
Had to increase the dosages to get an immune response and the higher the dosage the more the immune response was there and an artificial immune response against everything so cubic was for forced to reduce the doses to get an A Proper immune response and the dosage was too
Low to deliver the information to the body as I said it’s a kind of information the body needs information it was a too low doses it could really increase couldn’t really increase the dosage whereas Mna and beon they could use triple times four times more dosages
Than cure and this was enough to induce the immune response and was enough signal and there was really no um side effects on that so that was the reason why kurec failed in uh utilizing the covid vaccinations and that’s the reason why bch Monna did so well in that and
There a reason why cardaro got a Nobel priz this year you can see it here what I told you so Monna already used 100 uh microgram uh bondex 30 and we just 12 microgram it’s really the highest does otherwise U it’s too high and uh it’s not really
Getting a lot of side effects higher than that so that’s the reason well again we are really proud that we got the first GMP um um um approval like that and of course uh there are a lot of uh uh preclinical and clinical work um we started with
Oncology um that was uh uh more important to us in the beginning and then we switched to covid-19 vaccines you can see there were a lot of trials going on but uh we didn’t succeed we couldn’t get the approval there so again what’s also important to know that uh the production is always
The same it’s just the sequence you change so the production process remains always the same whether you do a vaccine whether do you cancer vaccine covid vaccine or you do some different thing or an enzyme like that it’s always the same process and that’s the beauty in it because RNA is like software
Go ahead why it’s not going ahead yeah okay another nice thing because I told you already uh it’s a quite of easy process and always the same process you can uh have a kind of printer of RNA that’s really interesting it’s a kind of device you can just type in the
Sequence you want to uh be printed out and the printer is printing out you have to put all the ingredients enzymes like that into the printer and then you get your RNA constructs in the end and one day you make an influenza vaccine the other day you make a covid vaccine the
Third day you make a prostate cancer vaccine that’s the thing and you can really um have it kind of Mobile station so if there’s an outbreak somewhere in Uganda in Africa a new covid outbreak or new other disease you can just Implement a machine there and you get get it
Printed out where the spot uh happens of this uh outbreak so that’s the print box um and uh we invented that uh and we are very happy that we could collaborate with uh Ellen Musk from Tesla because Tesla is uh building some very important building blocks of this machine um so
Therefore we met also Ellen musk coming to tubing and he’s really also interested uh into this and when we started Tesla collaboration we met him uh in Palo Alto and he was asking me why I should work with you uh we do cars we want to work with BMW and this kind of
Why should work with cure we say well Ellen it’s like flying to the Moon with us we do the same like you uh in Your Vision because we revolutionize medicine and therefore we need a printer and you have the technology to provide us with the printer so in cubec printer there’s
Tesla technology included there and um I think that’s the reason and we are just the only project outside of car automotive industry um is not dealing with anybody else uh than with uh with cure because he was really interested in uh fulfilling this um Vision so that’s a
Really interesting thing and you can see just on the picture it can be somewhere in the jungle you can have a solar energy uh module and then you can independently produce RNA yes and then the pandemic uh we know about already uh that um and again you
Can really do and you can see here depicted the proteins um they’re really different and that’s the reason why it’s so difficult to work with proteins and to make proteins because they are very diff different in the the size and also um in the shape RNA is always the same
As I said and why not use the body produce the proteins and not the machine so let’s come into the future and I think it’s a real disruption uh we we can see here because now we are in a situation that we can talk to the body
We can have a recipe to the body saying the body well you know um you might get cancer so we can have a biopsy of the cancer tissue and can see the antigens of the cancer so antigens meaning uh what of kind of recognition patterns the cancer cells have to be recognized by
The immune system and then we can really give the information to the immune system wow that’s a cancer cell this is how it looks how a cancer cell looks like and you have to be active against these cancer cells and if the cancer cells and that’s makes cancer very very
Difficult it mutates always so if cancer is mutating giving new information to the immune system you can just adapt the vaccine say well cancer is mutating it’s hiding you can you can you have to change um your weapons like this so and you can use also other RNA Technologies
Like crisper for example chrisper crisper RNA can cut off genan expression that’s also something very interesting uh or crisper RNA can um can have an entic f f function of RNA as irna can cut gene expression my micro RNA gives a lot of signals and you can use the
Messenger RNA as I told you so RNA can do a lot so and that’s the vision we have as I told you so cancer might be a kind of U disease you not only you’re not anymore dying off because you can always engage the immune system that the cancer
Cells they always have to uh to um to hide themsel or to do something against the immune response so cancer is growing because cancer has nothing to do it can just grow but if you can entertain the cancer cells that they can’t grow anymore that they have to defend
Themselves all the time therefore you can live with Cancers um and cancer is not really infecting or implementing the Orin which are U like lung uh like panas uh Orin which are which are necessary for your life it’s kind of entertainment you have to entertain cancer then it can’t grow
Anymore the other thing is Alzheimer we we don’t know exactly what happens in the brain but uh the older we get the more uh uh the more the more issues we have in our brain and the thing is also well maybe you can also interact with
That with the brain cells uh to stay healthy um and um if you see really what makes Alzheimer happening in the brain you can really defend it also using RNA U molecules and the nice thing in the end and that’s a really utopic thing maybe also aging because something
Happens to our body we age uh maybe you can also Implement like this that um the agent is is uh somehow um slowing down a bit more of wrinkles or things like that you know it as Cosmetics but I I don’t know but maybe something um as it’s a kind of
Information to the body and the body needs information how to prevent Aging for example what you can do against it that can also something uh very interesting happening maybe it’s um I word it 10 years back I was 2030 BBE it’s 20 40 but I think this is a really
Uh High chance that it will be like that you can also implement the Aging of course we all die it’s clear you can’t prevent death but again maybe you can die in a kind of healthy uh condition yeah I think that’s that’s uh that’s really um so I’m I’m really
Optimistic that we all see this coming up uh Force for ourselves because many many companies are involving uh China and all the other countries and a lot of new technologies will coming up like that and we have a lot of more knowledge about receptors about functions in the
Body and that’s the easiest way to Target those factors is the RNA technology which is available so therefore very Bright Futures thank you very much thank you I have one question to or maybe two very quickly because I remember uh I have to ask this because
That’s I think very I I believe very interesting you you you showed us the picture with Elon mask and that’s a situation when when you have to convince someone who is already conv convinced because they know something’s going on that they they there is a business there
Is a opportunity but when in the start I remember you told the story that you’ve been you you try you presented in front of the renowned uh scientists and they told you what it’s nonsense yeah when I was just a young boy coming from the University sitting here in a
Panel talking about uh the RNA thing um people really don’t believe me and there was a Nobel Prize uh winner sitting in the first row and he was really standing up uh in front of me and say it’s it’s what you tell here it’s completely what do you say
Against this you know it’s getting red in my face I say it’s not I see it because I saw it in mice I injected mice I saw it in a living living animal that it works and this guy says indeed no it’s uh it’s it’s it’s unstable he can’t because everybody thought RNA
Is really a molecule U which is not usable for any U treatment thing and the thing was really because of the unstability they have seen and they have observed but it really didn’t really dig deep enough to see that RNA is the first biomolecule it’s the most stable
Biomolecule what we have that was very interesting yeah and this is a message to young young scientist is to to be kind of stubborn in your pursuing your your goals and second example I I remember this is this could be the message for startupers again because I
Remember you told later on you’ve been invited by DARPA in USA to present something about these new discoveries and then happen something interesting you remember yes of course of course I remember well darar is a military agency of the US um so I I really didn’t know
Uh what it was then but I then I I went to to Washington to the uh defense Ministry really to the defense Ministry you have to go to a lot of security controls uh it’s really amazing um and I watch thinking wow what’s what’s going
On here uh and then I saw the Dara officer um um in in um with our project uh I had a phone call with him um but I saw it now in person and he had an uniform so he had really an uniform he was a military guy sitting there and I
Was sitting here as like uh on Putin’s desk you know he was sitting a long time long way apart from me and um I was telling you know how good we are because I I I I knew how I have to pitch on a positive way how good we are what what
Went well uh and and there’s a you know as as I’m I’m secting you know we can revolutionize and things like that and he was really uh looking very very angry to me and say and then he was really putting his hand on the table throwing the hands on it say stop the
Bullshitting stop the bullshitting I really want to know what didn’t went well because we at darer we fund only highrisk um signs we want to really see the risks and then we can speak about uh the chances but I want to see the risk what what didn’t went well I want to
Really tell me the truth here because also for me for my knowledge I want to invest money that you solve the problems it’s a solving problem things here um and I was somehow flipp and say okay um yeah we have we have some production issues Purity impurities for example
It’s it’s not easy to control we have to do more controls like that um anyhow we just have animal models we have to use clinical trials we have to get the right models in clinical trials cancer is very uh tough Target but vaccines um we can’t do because vaccines are all available so
It’s a really issue and say well let’s let’s talk about it how we can fix this and this was something um changed my life somehow really to talk also about uh the negative things um and really see how we can solve the negative things especially uh to agency like Dara I’ve
Never seen this before because the German and the U funding is always you know well yeah Milestone Milestone Milestone everything went well everything is good um and that’s a different uh think uh the flip side thinking and this I like very much that you really do the high-risk things talk
Openly to the officer and if things are not going well then I have trust and he he will support me because this exactly what he wanted they want to see really the the edges of the technology they want to see how far our technology can go because it’s very important for the
Military to know the impact of it and you can only know the impact if you see failures so that’s was very very interesting a good teaching to all of you um it’s important to cope with failures and to learn from failures and to see the edges how far we can go with
The technology okay thank you very much h um you will be you will have again chance to to talk or listen to hul Afternoon in the session of final session thank you very much and we are now starting those separate sessions that was the message actually for startupers never trust the guys who
Don’t ask for problems