Integration site analysis is becoming a critical tool in evaluating the safety of gene therapies, but how does it actually work, and when does it matter most? Michael Stump and Matteo Franco of ProtaGene break down the science, the risk, and the evolving role of CROs in this rapidly changing field.
In this episode, Michael Stump and Matteo Franco from ProtaGene explore the growing importance of integration site analysis (ISA) in cell and gene therapy. As viral vectors like lentivirus and AAV become more widely used, understanding where and how they integrate into the genome is essential for assessing genotoxicity and long-term safety. The discussion dives into how sequencing reveals integration locations, clonal expansion risks, and potential activation of oncogenes. They also highlight how tools like digital PCR complement sequencing as orthogonal methods that help enable precise quantification, validation, and new applications like vector integrity and copy number analysis. Beyond the science, the conversation explores the CRO role in supporting both early-phase discovery and late-stage regulatory needs, balancing innovation with regulatory expectations, and adapting to emerging modalities like LNPs.
The career corner brings a mix of honesty and humor, from chaotic CRO workdays to broken PCR capillaries and runaway lab mice, paired with thoughtful advice on navigating industry paths, building GMP expertise, and finding the right fit between academia and industry.
Lisa Crawford 00:00
All right, let's lock in, fam.
Jordan Ruggieri 00:02
Could always just use my name. "Jordan, something that we hear a lot from our guests."
Lisa Crawford 00:08
Is that better?
Jordan Ruggieri 00:08
No, should never use my name.
Lisa Crawford 00:24
Welcome to Absolute Gene-ius, a podcast series from Thermo Fisher Scientific. I'm Lisa Crawford.
Jordan Ruggieri 00:29
I'm Jordan Ruggeri, and today we are diving into integration site analysis and how CROs like ProtaGene are shaping this field.
Lisa Crawford 00:36
Our geniuses today are Michael Stump and Matteo Franco, President and Lead Scientist, respectively, at ProtaGene. . They share insights on genotoxicity, how they use digital PCR, and the balance between regulatory expectations and customer program goals.
Jordan Ruggieri 00:49
We hope you enjoy the conversation.
Jordan Ruggieri 00:55
Michael and Matteo, thank you so much for joining us on today's episode of Absolute Gene-ius. Could you maybe start with just giving a background about yourself and a little bit about ProtaGene as well?
Michael Stump, PhD 01:07
Sure. Thank you, Jordan. It's nice to have us. My name is Michael Stump. I've been to the President of ProtaGene for about 18 months, but in the industry about 25 years. ProtaGene is a small CRO that really focuses on two main areas. We focus on CMC mass spec design, and then also on the cell and gene therapy side, we focus on the ISA, integrated site analysis.
Matteo Franco 01:30
Matto Franco, nice to meet you. I'm the Lead Scientist here at the Burlington site. I've been mostly dealing with integration site analysis, but I've been with the company since 2018. I moved to the U.S. when we decided to open a site here, and I've been here since working on mostly on integration site analysis and molecular biology capabilities.
Jordan Ruggieri 01:51
That's excellent. Yeah. Can you talk a little bit about what is integration site analysis and what are some of the considerations for customers that might be looking to do that?
Matteo Franco 02:03
Of course, yeah. So, integration site analysis is a field that is has become more and more relevant the more viral vectors came into play, into the gene therapy field. It's basically looking at the genotoxicity of these viral vectors when they're administered. Our job here is to basically get the samples, sequence them, and then determine where the integrations happen. So, for instance, in case of a lentiviral vector, where you have an active integration mechanism, you'll find a lot of integration sites. So, you want to make sure that they integrate into the genome in safe spots, do not activate any oncogenes or the likes. So basically, that's a metric that helps you during, you know, your clinical trial to determine whether your therapy is safe or not.
Jordan Ruggieri 02:53
Interesting. I guess we've never, or at least I haven't thought about this, you know, we do and talk a lot about, you know, the vectors themselves and creating them and getting them in the virus. But you know, once you once you actually get past the quality and some of the, you know, the look at the vector and the and the virus itself, actually, what happens within the subject. Seems like it would be a really critical area to dive into and make sure that you have an understanding. I mean, is it just looking at those integration sites? Just making sure that it's, you know, not incorporating in areas you don't want it to? Are there other aspects that you look at once it actually gets into a subject and kind of post that, you know, initial manufacturing and kind of safety check into your maybe early phase clinical research?
Matteo Franco 03:46
So the main readout out of integration site analysis is the location where the integration happens, but also the relative frequency. So, in terms of, like, all the reads that we cover from the subject how many are integrating there. So you then able to establish whether you have also called clonal expansion. For instance, a single integration event then led to the multiplication of cells, and that, you know, could be linked to a problem. It's not a direct connection by any means, but it could be, you know, a warning. But you know, we're talking about sequencing. So you have a lot of data that you can dig deeper into. So you can look at which part of the vector integrated. Normally, lentis integrate as a whole, but AAV is from the recombination, so it can be any part of the vector really. So for instance, you don't want to have a promoter that integrates near an oncogene. So that's one thing that you can check and, you know, make sure that it doesn't happen. You can, you know, just also in terms of like topological integrations, you can, you can see what is the distribution across chromosomes. You can see the distribution nearby cancer genes. If there's an integration hotspot that is difficult for your vector. Sure. So there's a lot of other interesting quality attributes, again, you can search. I mean, its still early stages, but like people have started to delve into a long read, for instance, integration site analysis. So that gives you a better idea of the integrity of the vector when it integrates, or if it persists episomally how they persist. There's a there's a lot of data that you can extract out of these.
Jordan Ruggieri 05:27
Taking maybe a step back even and talking about ProtaGene and your approach. Can you talk a little bit about, maybe what a CRO is, and some maybe considerations for maybe some of your potential customers that might be looking to have this research done? What exactly do you do to help make sure some of these things turn out well, or as best as you can expect?
Michael Stump, PhD 05:51
So a CRO is an interesting term. A CRO is a contract research organization, and somehow that gets lumped in in the industry. Sometimes CDMOs are included that with the manufacturing piece as well as the testing piece. So within the CRO world, ProtaGene is basically an advanced testing platform. So we test both at the early phase and late phase. So, from CROs, they can be one-stop shops where they can run a whole suite of assays for a lot release, or they can do early phase for design and different pieces along the way. ProtaGene fits into that puzzle where we're what I would call a niche CRO and by niche, I mean we only offer some of the assays you would need for maybe a lot release, but we really focuses on advanced characterization. So if you come to us for basically on the CMC side, we could be there for early phase and characterize. But we can also support late phase and GMP for lot release and advanced stability studies. On the cell and gene therapy side, same thing again. We can be there in the early days to start the assays to show if there's any issues up front, and then we can go all the way through commercial phases and help on the back end as well for lot release. And in fact, we actually are just becoming a CLIA lab, both in the U.S. and Europe, to support CLIA for ISA, which is very new, we're supporting some of the first companies that have done this in the industry.
Lisa Crawford 07:09
So help me understand, is there a certain kind of viral vectors or a certain product or a certain disease area that people are more likely to use your services? Or is this something that kind of applies to everyone in the space? Depending on, you know, their interest in going deeper?
Matteo Franco 07:27
So normally, we, our customers, are more into the gene therapy as a whole. We've seen mostly viral vectors, a lot of lentiviral vectors, a lot of AAV, a lot of retroviral vectors. It also depends on the trend of the industry. We've seen a lot of LNPs popping up lately at the end of the day. You know, we try to evolve with the market as well, right.
Michael Stump, PhD 07:48
Yeah. So basically, it comes down to what do you need? Is it, do you need to support lot release or do you need characterization for early phase or advanced characterization for filing? So for us, we could do both. For the CMC side really does the characterization piece, which is more of a nice to have. In some cases, it's a need to have in other cases. The ISA piece that we do, and that's kind of an interesting part of the industry right now for us, if you want genotoxicity, this is the best way to do it. And still in the industry, it's a “nice to have”, not a “need to have.” But if you have a severe adverse event, then it becomes a need to have. So that's kind of where we're at. So upfront, some clients are looking at a risk mitigation strategy where we develop the assays and we're ready for the severe adverse events. And in some cases, they do tests about 10% of samples just to be safe.
Jordan Ruggieri 08:34
Can you elaborate a little bit on genotoxicity? What is that and how could it impact some of these developing therapies?
Matteo Franco 08:43
Yeah, of course. So in terms of genotoxicity, we mean toxicity for, you know, the subject as a whole, arising from a genomic level. This is where integration site analysis comes into play. We make sure you know that, like, the integrations of these therapeutical vectors don't impact the subject in any kind of way. So, for instance, if you have, you know, a lentiviral vector integrates multiple times into the genome after sequencing, we determine whether this integrates and if there's a potential for a severe adverse event. Or vice versa, if we have a severe adverse event, and we want to make sure that it was not the vectors fault to get this result. So again, we use integration site analysis to determine, is it the vector that activated this oncogene, or was it something else?
Jordan Ruggieri 09:31
How does ProtaGene look at, let's say technology acquisition, right? So you have your kind of set protocols and some of your methods that you support. How do you evaluate when there's a new technology that you should integrate in, a new method, or you need to bring in some type of new equipment to support customer needs?
Michael Stump, PhD 09:55
There's kind of a dichotomy of differences in the industry. So from the FDA point of view and the regulatory agencies, they want something that's old, tried and true. They don't care how old it is. If it's got 20 or 30 years of history, fantastic. I would say, in the cell gene therapy space, in the last few years, it's kind of the opposite of that. Whatever is brand new and shiny, they want it instantly. So, it basically comes down when you're looking from an R&D perspective, especially in the new cell gene therapy space, and even large molecules and ASCs, they want the latest, greatest instruments that come out in the market, which is what, like Thermo and other companies support. For a CRO, we're kind of stuck in between, right. It really is, is we want to use the platforms that are most important to our clients and to support the science. So, from a CRO point of view, we try to be agnostic. We will use whatever works best. So what usually happens for us is when something new technology comes out to the market that's getting a lot of buzz, until our clients we can show that more than two or three need it, then you don't make the investment up front. So, we have a technology council that whenever our either our BD representatives or we send the scientists to conferences where they'll come back and they'll say, "Hey, we saw this new piece of equipment from Thermo that can do X, Y and Z." So then we'll take a look at that. And as soon as we have two or three clients that say, "Hey, we really want this," and we get to the point where we get to contract and it works, then we'll look to make the acquisition. The good side is, we might be slow to adopt, but usually in our space, “Why have one? We can get to at twice the price,” is the motto. So usually, in CRO world, you always buy two or more, because if one breaks, you can't ever afford to be down. So we might, we might be slow to adapt than when we do usually invest pretty heavily in the space where it's applicable.
Jordan Ruggieri 11:35
No. It makes sense, and we've had conversations like this before as well. Whereas you know, FDA, like you said, tried true, 20,30, years, they want something that's there, but that's not always where the the actual, you know, teams doing the research live in terms of trying to figure out new methods or new ways or new approaches to make sure, you know, targets are safe, or try something new, right? And be kind of on the forerunners of innovation for the space. So it's always a balance. It sounds like a really good balancing act that you have with the with an acquisition team and a technology team and looking at customer need. How do you approach looking at these different technologies? So say like, you know, we love PCR, we love qPCR, dPCR here at Absolute Gene-ius as well. How are those technologies utilized in your space?
Matteo Franco 12:32
There are definitely a lot of different ways that we can utilize them. That also ties into the previous question, I think, because sometimes you don't need a new instrument to perform a new assay, right? So I feel like, especially now in, you know, with the with digital PCRs, there's always something new that people develop. For instance, I think that I came across recently was, then also gained a lot of traction at ASGCT was the use of dPCR to assess the integrity of a vector. Because now with dPCR is very easy to, you know, multiplex. A lot of people are starting to experiment, you know, with, with the multiple targets that you can use. So you can use multiple primary probe sets to that span across the vector and then assess the integrity from there. You know, you can use them for vector copy number. We use them for replication competency by distribution transgene expression. Like they're very, very versatile, and the multiplexing capabilities also in in general, like simplify our work. They make it way easier, and it gives you a better readout at the end of the day. Because back in the day, at least, most of the PCR analysis we were used to do on qPCR were a single target, when now we can just throw a reference in there, and it's super easy to do.
Jordan Ruggieri 13:56
That's cool to hear. I mean, it sounds like, you know, between the different technologies, you kind of use them to answer different levels of questions that you or your clients might have, but also in new ways to make things a little bit easier, faster, maybe less expensive, and on everybody's end. So rather having to maybe send something through to sequencing, you know, where might take a little bit longer or be a little bit more expensive, you can use something like digital PCR for that, you know, making sure that it's, you know, the right vector and, you know, and just using it in different ways right to help make sure that the questions are answered properly and with enough confidence to keep things moving forward. Is that, is that accurate, an accurate statement?
Matteo Franco 14:50
Very. Very. Actually, that's a very good point, because they can also be used as an orthogonal method to sequencing. Like, do we want to really make sure that an integration site? Really happen at that place. You know, we want to know exactly the quantity, because maybe sequencing, you know, is still a relative metric, right? So we want to know exactly how many copies you have confirmatory dPCR, why not. Same thing with gene editing. Do you want to make sure that a certain edit happened on a certain site? You can also throw it on the dPCR. So it's a very powerful instrument for us. And you know, as you said, you can be, can be used in a lot of different ways, also to complement what we already offer.
Lisa Crawford 15:29
When a client comes to you and they say, you know, "I have XYZ problem, or I need to get XYZ done". How much of what you guys do in response is, like, pretty cut and dry or something they ask for, and how much of it is problem solving, like you just said, trying to integrate these different technologies?
Michael Stump, PhD 15:46
That's a great question. And to answer that, there's a wide variety. So, I think from the CRO world, I think to answer your question, I'm going to probably take a different approach, and then I'll answer in the back end. So, I think there's about four or five factors that people look at when they select a CRO. One of them is, what is the quality that you need to submit to the agencies to check a box. The next one is, is the science really strong and supporting that? The next piece is probably turnaround time. How fast can you turn this around? And then communication is also a piece. How well do you support this so we know what's going on, and the other one is price. So you kind of blend that all together, and then it depends on what, who is asking that question. Because we work from everybody from large pharma all the way to a startup, right out of the university. So, depending on who it is, they're going to have different levels of expertise. So, it's not to give a hard time to the startups, but typically they don't always know the whole process, or whatever a CRO does. So when they come to us, they think they have an idea of a problem, and in that case, CROs we really do spend a lot of our time of coaching team explaining to them, both the regulatory piece, the science piece, and everything we do, and everything in between, we have to do a lot of hand holding there, which is what we like to do. We enjoy that. When it gets to some of the larger companies, the larger pharma that have been at this game for a long time, they pretty know much exactly what they want, and in some cases, we're even pushing the science together in partnerships where we're taking the technology we think we have it figured out, we'll do something new together, and then we publish. So, it really depends on the audience and who's asking the questions, but overall, at a CRO we do, spend probably half our time coaching clients of what the science is and how to best integrate that, a,nd there's also a fine line there with quality, too. As a CRO we're not trying to tell you how to file, file, your quality reports. That's up to you. What we really do is just try and show you what we think will work best in any given situation.
Jordan Ruggieri 17:35
What do you see as, you know, what do you think this field looks like in the next couple years? What's, what's exciting? What's, what's coming up, and it's really something that you're really eager to get into the lab or get into work and keep pushing forward?
Michael Stump, PhD 17:51
So I would say, in a previous life, before I joined ProtaGene, I've worked in the cell gene therapy at a very large group CRO and I see this very well. So, I think there's very much challenges these days in the cell and gene therapy space. I think everybody rushed out and thought, “We can solve a lot of problems.” And it's really unfortunate, because at the last ACGT conference, it was well known that everybody was starting to celebrate some significant wins, like we're really starting to see the wins, but we never asked the original question is, “How are we going to pay for this?” And because that question was the elephant in the room, it's like everybody kind of knew was going to hit, I think 2024 late 24, 2025 was year where everybody that we couldn't avoid that question anymore. So the cell and gene therapy space is really, really going to be challenging right now. I think everybody's looking at liquid nanoparticles and different things of what they can do to get away from the different viral vectors. But unfortunately, there's enough in the pipeline with viral vectors that we really have to play some of this out. Overall with ProtaGene, we would love to be able to support, you know, the genotoxicity and advanced platforms for this cell and gene therapy space. But like I said, it's really challenging. Overall, that said, I think also on the ADC size and large molecules of MAVs, there is a ton of resurgence in there, because as the cell and gene therapy has dipped down, now you're seeing this influx now, with ADCs and AOCs and different modalities coming back into play to fill that gap and go there. So, from our point of view, as CRO we are agnostic, our CMC side can support either modality. ISA is favored more to selling gene therapy, but we have enough assays to balance out what's going on the market. But over the market itself right now, I just it really is a shame the cell and gene therapy space, you know, with all the great wins we have, I just wish we could figure out the payer piece.
Matteo Franco 19:35
That's a very good point. And I think in terms of like science, like, our key will be to be ready to adapt to whatever comes next. Because, as we mentioned earlier, like LNPs are becoming more and more central. So, we to adapt and provide basically an analysis that can better fit those kind of vectors. That that's pretty much it. Like we enter in general, bioanalytics and sequencing will still be essential. We will just need, basically, to adapt the current methods to better fit the LNPs, especially in terms of like sequencing, but yeah, in terms of molecular biology, we're pretty much there.
Lisa Crawford 20:17
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Jordan Ruggieri 20:23
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Lisa Crawford 20:37
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Jordan Ruggieri 20:51
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Lisa Crawford 20:58
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Jordan Ruggieri 21:17
And now let's get back to our conversation.
Jordan Ruggieri 21:23
All right, I'll pass you over to Lisa for some career background and career corner time.
Lisa Crawford 21:28
Yes, we're going to get away from a little bit of the science and talk more about you guys and both your backgrounds. I actually have a question for both of you that I haven't asked anyone yet, and it occurred to me, because I think the space, especially, you know, CRO, CDMO if you're not in that industry, I think it can be pretty opaque for people to understand kind of how it all works, right? So I was wondering if you, both of you, separately, can kind of walk me through what a typical day looks like for each of you, since you're also in such different positions. Just what it is that you come into work an average day, what kinds of things do you do?
Matteo Franco 22:03
It's hard to answer, in my opinion, because it really depends also on the like, we rely a lot on the client interaction, right. So one day can look very different from the other, but in general, you know, most of my days are spent in internal meetings, as per usual, where we are, you know, we align on certain like projects, or, in my case, also developments, because usually I'm also involved in those. And then that's usually what happens in the morning, because we also interface with our German sites. So that's when usually that we managed to, you know, overlap a little bit. Another part of my day is, definitely, you know, working on the client projects, handling communication with them, preparing results, slides, reports, instructing the lab on what to do, any planning that might require, or anything. And then I also am involved in, sometimes in the BD calls where, you know, where, when I'm there as a subject matter expert to support our RBDs in, you know, getting more clients, managing current ones as well.
Lisa Crawford 23:12
So are you ever in the lab, or you're more of a supervisory, strategic?
Matteo Franco 23:16
I'm more of a supervisor. Sometimes I can end up in the lab, especially, you know, mostly for supervisor things. Showing up there, check on certain projects, devices or analyses. In rare cases, I'm also the one pipetting, but I usually keep that to a minimum.
Lisa Crawford 23:36
When people are on vacation, maybe they got to get you in there?
Matteo Franco 23:39
When you need, like, several operators, for instance. And you know, some people are out and I need to step in. But you know, it's more rare. I usually am more of an office worker, let's say.
Lisa Crawford 23:50
Michael, what about you?
Michael Stump, PhD 23:51
So basically, I've been in executive management for over 10 years now, in the industry 20 plus. So in the executive management role, I would just say my job is a controlled, chaotic firefighter. That's all you do is put out fires. And I'm convinced people that do this for this longevity, we like the challenge. Because if I went to large pharma and worked in a similar role, I'd work on one or two molecules for five years. I think the reason people select a CRO world is they love the variety. I would think in one year alone, I worked on 139 different compounds in a previous life, just to give you perspective. And so for people who choose to the CRO world, I think they really just love the variety and the action. And there's always this constantly stuff happening, and it's always a balance of timelines to get what we need to meet that and how to do the best science possible given the timelines. I think the hardest part in the CRO world is a lot of scientists coming out want to do perfect science, and at the end of the day, you have to balance that with science that is strong enough to meet a deadline. Doesn't mean that we'd ever for one second, sacrifice the safety of any subjects, it's more along the lines of scientists tend to want to wait till everything's perfect, when we already have an answer that that checks the box and you're good to go. I think that's the biggest challenge I have in the CRO is convincing my scientists to to, you know, we want to do the best science possible. We get there, but we can't overdo it either, because the timelines and the cost just doesn't, is prohibitive to that factor.
Lisa Crawford 25:21
Another question that I like to ask people is, if you were to run into someone at a conference or somewhere, you know, younger, just starting to get into science in this industry, what is something that you maybe wish that you had known going into this, that you would share with them, just to kind of guide them and maybe some advice for them as they get into this?
Michael Stump, PhD 25:40
So to me, the way I explain it is, if you want to get in this space, everybody wants to work in large pharma. And I would say is that doesn't, there is no clear path coming out of the university to work in large pharma anymore. You have to do your stint or pay your dues, basically in the CRO world. Because the way the industry works right now is, you don't have any experience, and you really need to get that GMP. So my advice to the young kids is start working for a CRO and gain your GMP experience and learn the techniques. Because there's two pieces of what we do, there's the science piece, and then there's the documentation of the science piece. And they're two very different things. And I can take a lot of really good scientists that are R&D scientists and can't do the documentation. So anybody that wants to get in the space, I would just figure out what you're really good at. And if you want to do the science, and that's okay, then you have to stay on the R&D side more. But if you really want to do the impact and help the subjects and the most you can, then you really have to figure out the GMP piece and learn the documentation, which is a whole different thing.
Lisa Crawford 26:33
Can you explain GMP?
Michael Stump, PhD 26:41
So there's different phases of the FDA approval process. There's preclinical which is early phase. It doesn't need to be GMP. Some people say GXP, because there's good laboratory practices, there's good scientific practices, and there's a couple of the things in there too, good clinical practices, GCP. There's everything. So GMP is the kind of the main one. Whenever you get to clinical phases, you have to have a manufacturing process that's aseptic and guaranteed. So, you have to do things under GMP processes. So all CROs, you know, unless you're an early phase, you may not deal with GMP, but for most of us, we have to deal with GMP. It's getting to be more and more.
Lisa Crawford 27:18
Thank you for clarifying.
Michael Stump, PhD 27:21
Yeah, sure. No problem.
Lisa Crawford 27:23
Yeah. So Matteo, do you remember the question?
Matteo Franco 27:25
Yeah, I do, but I feel like I am a little bit on extreme case, because I'm still working for the company that I joined right after my studies. So I mean, it ties a lot into what Mike said. I think you need to find what you're good at and what you, or at least what you think you're good at, and then explore from there. Because, you know, like, academia and industry are very different worlds. You really need to figure out what you're best at. Like, I have some friends that are, like, diehard academia people. They like the environment, they like writing grants. They like being in the lab the whole day. That's not me, personally. So maybe people that are more like me, that the you know, they want to have a more fast paced job, like client interaction or something like that, then maybe the industry, especially a CRO could be more of, you know, a better fit for them. So yeah, I would try to see engage which you're like, which is your main interest at the end.
Jordan Ruggieri 28:27
It's all good advice.
Lisa Crawford 28:29
So, yeah, I think we just have one last set of questions, unless Jordan, there's anything else. We like to ask each person, what is a memory you have of maybe your most embarrassing moment when you were coming up through the ranks, maybe in the lab, you know, maybe some other place, and then also, you know, a crowning achievement, or, like, a great memory that you have of something that you feel very proud of?
Matteo Franco 28:53
So an embarrassing and great memory.
Lisa Crawford 28:55
Well, we like to balance.
Michael Stump, PhD 28:57
Oh, I have a lot of embarrasses, more embarrassing than great. So that's easy. I think for me, the most embarrassing one is I had just become director of a lab. We had some Japanese, a company from Japan that came and they didn't speak any English, and my job was to tour them. And so I naturally talk very fast, and I'm very animated. So when I went on the tour, I talked really slow and simple, but I didn't tell the lab this, and they didn't know, and so they thought I was being degrading and racist to them and reported me to management. And then had to sit down with a team and explain that they didn't speak English and they didn't know. So for me, I think that was probably the most embarrassing point is, is once a team understood, and I explained that everything was fine, but it was, it was a learning moment for me. When you tour labs, you tell everybody what's going on and inform them. So I think that was kind of embarrassing. I think the my greatest achievement working in the cell and gene therapy space, and there’s probably two different stories but very similar, is being, getting, helping one come to get the first in the market for solid state tumors and developing cures, where you know that your survival rates went from people going to hospice, that within 30 days, these people are not only survived hospice, but they have true cures, and get back to their life within two months. And being part of those teams where, you know, you have a GMP run coming off at 10 o'clock at night on a Friday night, and you have to have three rounds of coverage, and you make sure the staff is there, and they're able to get that the lot approved to have those outcomes. And just working through a process where that becomes somewhat seamless. It wasn't seamless, but it was a process that we developed. But just knowing that you worked on molecules that truly save people's lives is really hard to beat.
Matteo Franco 30:52
My great memories are more or less that. Like, I feel like the great thing about like working for a CRO is that, I mean, sometimes you get into anonymity because, like, sometimes you know they you're providing a services. So you know, some clients are like, “Okay, you provided the service, bye.” But other times, the you know, they share the results with you. And it always, it does feel like what you do actually matters, right. Because you get notice that maybe the treatment was successful and you worked on the treatment. So you realize how much like it means. Like what you do means for maybe, you know, people that are have, like, very bad disease, or, you know, they somehow managed to survive at the end, and so it makes you really proud of what you're doing. And in terms of embarrassing moments, I guess. I mean, I was very green back the other day, but I remember during my bachelor internship, I was part of the retroviral lab back in the University Hospital of Bologna, and we used to have a very old piece of equipment. It was a light cycler for PCR. It was so old that it still had, like, Windows 95. And on top of that, you know, like nowadays, qPCRs are on a plate, super easy to handle. That was a light cycler, so it had glass capillaries. So what happened, basically, was, like, you know, I was being tutored, like they showed me how to do the qPCR, you know, like, “Be careful, capillaries break.” Of course, course, no problem. So I go and get these samples, and they're like, “Remember, this is the last of the sample. We have be extra careful.” Got it piped the reaction run the cycling, get absolutely no results. Open the lid. Everything completely broke with all of the reaction at the bottom of the light cycler. So it was also a mess to clean, one of my first forays into the lab, and what was also probably one of the most embarrassing. But at least the staff had a good laugh. I didn't on the time.
Lisa Crawford 33:05
When it's you, you go into the back and just have a moment to yourself after that.
Matteo Franco 33:09
Now, well, now looking back, I laugh at it, but
Jordan Ruggieri 33:11
I love that question, because makes it makes everybody seem human, right? We've had so many different examples of embarrassing things and things blowing up. I have a bunch in the lab too, and everybody is human. Everybody makes mistakes and still wind up in great places, right? So it's always fun.
Michael Stump, PhD 33:29
The other one I could probably talk about is the one I lost a mouse.
Lisa Crawford 33:34
I'm assuming you mean like a mouse, not,
Michael Stump, PhD 33:37
Yeah, mouse, an actual mouse, with an animal studies. We were my wife and I had a company where we were doing an anthrax vaccine, and we had to inject 40 mice, and we had to bleed them first to get a baseline and then inject them. And on mouse 39 after 16 hours of that process, with the last one, I go to bleed the mouse, and it jumps out and escapes, and it's running through the lab. And my hands on my knees at two o'clock in the morning trying to chase down the mouse, and it took me about 30 minutes to catch before we finally could get the mouse.
Jordan Ruggieri 34:09
Michael, Matteo, thank you so much again for this amazing conversation. I learned a ton and had a lot of laughs along the way. So thank you very much for your time, and we'll, we'll, we'll catch up soon.
Michael Stump, PhD 34:20
Yeah, and just thank you for your time and your interest in ProtaGene and just our life story and how the CRO industry works. It was great fun. So appreciate you.
Matteo Franco 34:29
Yeah, appreciate so much. Thank you for the opportunity. It was very nice to talk to you guys.
Lisa Crawford 34:34
That was Michael Stump and Matteo Franco, President and Lead Scientist, respectively, at ProtaGene in Burlington, Massachusetts. We've got more great conversations and new episodes dropping soon, so stay curious and we'll see you next time this episode of Absolute Gene-ius was produced by Sarah Briganti, Matt Ferris, and Matthew Stock.
Jordan Ruggieri 34:51
Products mentioned in this episode are for Research Use Only, not for use in diagnostic procedures.