
4.12.22-Health-Science-Startups-Kano-Therapeutics

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Interactive transcript
FLORIS ENGELHARDT: I'm completely starstruck. I'm the co-founder, Floris, from Kano Therapeutics. We are four months old. So end of last year, I was still a post-doc at MIT at Mark Bathe's lab, and you guys here are sitting over there, Kytopen, Volta Labs, Cellino-- these are the people I was looking up to. You're already role models-- just wanted to say that.
I would like to talk to you about single stranded DNA plasmids. Eric already mentioned that before, and how we can use them in CRISPR therapeutics. CRISPR has come a long way, being a gene-editing tool for size-specific gene knockouts, and when we look forward into the future and what we can do as the next steps, all we ask is how can we do site-specific gene knock-ins. And when we think about site-specific gene knock-ins, we need to think about a new player that comes into our drug, and that's a synthetic DNA molecule.
Whereas for CRISPR gene knockouts, we already have our gene-editing tools, we have the Cas proteins, they are innovative we have different delivery modalities coming up, with electroporation, microfluidic approaches, encapsulation technologies-- the question now is, what do we do with the gene vector? Why do we treat the therapeutic agent that is actually the information carrier still as a raw material? Can we do more there?
And that's where we come in. We looked at different applications from leading labs, and all they say is switch from double-stranded DNA to single-stranded DNA. Like everyone today here talked about DNA plasmids, and I always compare that in terms of comparing pasta because it's the same material. We have compared fusilli, which is much more rigid and could be depicted by double-stranded DNA, to something like single-stranded DNA being only one strand, being very flexible, and most importantly, it is engineerable because we can engineer the three-dimensional structure into it.
So already, the current science says that double-stranded DNA has safety issues, which can be solved when we use single-stranded DNA. We get high energy knock-in efficiency. We get higher safety profiles, meaning the life cells are just in higher numbers there.
The problem is that we enter into huge manufacturing bottleneck. The reason why single-stranded DNA is currently only used in academic approaches and not in industry is because chemical synthesis and enzymatic approaches can simply not yield the amount and quality of DNA in gene lengths that are needed for gene therapy approaches.
So that's where Kano comes in. We said, OK, if we need large amounts of clinical-grade DNA, why don't we use biotechnology? Why don't we use a fermentation-based approach? So anyone who works with DNA plasmids knows we can grow double-stranded DNA in bioreactors. Now we use a system that includes a bacteriophage-- so normally, a virus that infects bacteria.
But here, we have the bacteria, and you see that on the electron microscopy image, the bacteria that actually is the factory that produces large amounts of single-stranded DNA and then puts them out into these filamentous particles that simply envelope. Normally, they're the bacteria-- like the genome of the phage, but we changed that. We changed that so it envelopes our custom synthetic DNA molecules. We can already produce between 1 and 10 KB, and we can already produce milligrams of DNA. That should be enough to move on and enter into collaborations.
And that's where we are now. We want to innovate around the message and not the messager. We know that there are a bunch of people out there that focus on delivery methodologies and focus on new kind of therapeutic pathways so that we can tackle. We're the ones that want to build this gene vector platform that can then go into different electroporation, microfluidic approaches. And that's where we already work with Eric Smith of DFCI.
But then we can go even further and say how about in vivo approaches. Where can we actually adapt our single-stranded DNA there? I am here today with my co-founder John Vroom, who sits somewhere there in the back, and we would later be at our phone booth, so if you have any questions or any remarks, please come visit us and talk to us. Thank you.
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Interactive transcript
FLORIS ENGELHARDT: I'm completely starstruck. I'm the co-founder, Floris, from Kano Therapeutics. We are four months old. So end of last year, I was still a post-doc at MIT at Mark Bathe's lab, and you guys here are sitting over there, Kytopen, Volta Labs, Cellino-- these are the people I was looking up to. You're already role models-- just wanted to say that.
I would like to talk to you about single stranded DNA plasmids. Eric already mentioned that before, and how we can use them in CRISPR therapeutics. CRISPR has come a long way, being a gene-editing tool for size-specific gene knockouts, and when we look forward into the future and what we can do as the next steps, all we ask is how can we do site-specific gene knock-ins. And when we think about site-specific gene knock-ins, we need to think about a new player that comes into our drug, and that's a synthetic DNA molecule.
Whereas for CRISPR gene knockouts, we already have our gene-editing tools, we have the Cas proteins, they are innovative we have different delivery modalities coming up, with electroporation, microfluidic approaches, encapsulation technologies-- the question now is, what do we do with the gene vector? Why do we treat the therapeutic agent that is actually the information carrier still as a raw material? Can we do more there?
And that's where we come in. We looked at different applications from leading labs, and all they say is switch from double-stranded DNA to single-stranded DNA. Like everyone today here talked about DNA plasmids, and I always compare that in terms of comparing pasta because it's the same material. We have compared fusilli, which is much more rigid and could be depicted by double-stranded DNA, to something like single-stranded DNA being only one strand, being very flexible, and most importantly, it is engineerable because we can engineer the three-dimensional structure into it.
So already, the current science says that double-stranded DNA has safety issues, which can be solved when we use single-stranded DNA. We get high energy knock-in efficiency. We get higher safety profiles, meaning the life cells are just in higher numbers there.
The problem is that we enter into huge manufacturing bottleneck. The reason why single-stranded DNA is currently only used in academic approaches and not in industry is because chemical synthesis and enzymatic approaches can simply not yield the amount and quality of DNA in gene lengths that are needed for gene therapy approaches.
So that's where Kano comes in. We said, OK, if we need large amounts of clinical-grade DNA, why don't we use biotechnology? Why don't we use a fermentation-based approach? So anyone who works with DNA plasmids knows we can grow double-stranded DNA in bioreactors. Now we use a system that includes a bacteriophage-- so normally, a virus that infects bacteria.
But here, we have the bacteria, and you see that on the electron microscopy image, the bacteria that actually is the factory that produces large amounts of single-stranded DNA and then puts them out into these filamentous particles that simply envelope. Normally, they're the bacteria-- like the genome of the phage, but we changed that. We changed that so it envelopes our custom synthetic DNA molecules. We can already produce between 1 and 10 KB, and we can already produce milligrams of DNA. That should be enough to move on and enter into collaborations.
And that's where we are now. We want to innovate around the message and not the messager. We know that there are a bunch of people out there that focus on delivery methodologies and focus on new kind of therapeutic pathways so that we can tackle. We're the ones that want to build this gene vector platform that can then go into different electroporation, microfluidic approaches. And that's where we already work with Eric Smith of DFCI.
But then we can go even further and say how about in vivo approaches. Where can we actually adapt our single-stranded DNA there? I am here today with my co-founder John Vroom, who sits somewhere there in the back, and we would later be at our phone booth, so if you have any questions or any remarks, please come visit us and talk to us. Thank you.