Absolute Gene-ius

Almost a virus – how AAV powers modern gene therapy

Episode Summary

In this episode, the hosts sit down with Dr. Dan Mitchell of Matica Biotechnology to explore how viral vectors are engineered, analyzed, and manufactured for cell and gene therapy. The conversation spans CDMO workflows, AAV biology, and the critical role of qPCR and digital PCR in ensuring safety, quality, and performance.

Episode Notes

Viruses are not always something to fear; they can also be tools to heal. This episode looks into this positive side of viral biology.

Dr. Dan Mitchell, Senior Director of Analytical Development and Quality Control at Matica Biotechnology, joins the show to unpack the science and strategy behind viral vector manufacturing in a CDMO environment. He explains what CDMOs do, how they support cell and gene therapy programs at every stage, and why AAV has become such a powerful delivery vehicle. Dan dives deep into analytical development, describing how technologies like qPCR and digital PCR are used to quantify viral genomes, assess empty-to-full ratios, detect residual host cell DNA, and identify rare recombination events. He also discusses how sequencing, infectivity assays, and orthogonal analytics come together to ensure safety, potency, and regulatory readiness.

In Lisa’s Career Corner, Dan traces his path from marine biology curiosity to high-containment virology labs, pressure suits included. He encourages young scientists to get into the lab early, embrace failure as learning, stay curious and find the patience it takes to succeed in science.

Episode Transcription

Jordan Ruggieri 00:00

No pressure, everybody. This is all, this is always the hardest part is that, is that countdown and then you get that little bit of nerve and its, but it's all good.

 

Jordan Ruggieri 00:21

Welcome to Absolute Gene-ius a podcast series from Thermo Fisher Scientific. I'm Jordan Ruggeri.

 

Lisa Crawford 00:26

And I'm Lisa Crawford, and we are so excited to bring you today's genius, Dr. Dan Mitchell.

 

Jordan Ruggieri 00:27

Dan is the head of analytical development and quality control at Matica Biotechnology, and he boasts nearly 20 years of experience in the molecular biology space. We loved learning about the unique aspects of working for a CDMO, as well as learning about cell and gene therapies.

 

Lisa Crawford 00:48

One might say that their vectors are viral in the best way possible.

 

Jordan Ruggieri 00:53

Good one Lisa. Now, now let's get to today's Gene-ius. 

 

Jordan Ruggieri 00:56

Dan, thank you so much for joining the Absolute Gene-ius podcast. We are thrilled to have you here and in some of our background conversations, really, really excited about some of the things you and Matica are doing. Could you briefly introduce yourself and your role and a little bit of how you came to be working at Matica Biotechnology?

 

Dan Mitchell, PhD 01:18

Yeah, absolutely, Jordan. First off, thank you and your team for inviting me to participate. Very happy to be a part of your podcast. So thank you. So yeah, my name is Daniel Mitchell. I am the Senior Director of Analytical Development and Quality Control here at Matica. I joined in November of 2020 so I'm just about five years here at Matica at this point.

 

Jordan Ruggieri 01:40

That's awesome. Can you tell us a little bit about Matica, and then what does, what does Matica do?

 

Dan Mitchell, PhD 01:44

Yeah, so with Matica, we are a CDMO. We specialize in cell and gene therapy, primarily viral vectors. Lentivirus, adenovirus, AAV. We provide services to our clients to develop either processes and or analytics and manufacture their material, manufacturing different lots of their material, and putting it through QC testing and ultimately release for them to use for their program regarding, regardless of what phase they're in. You know, some are early phase some are preclinical, some are phase one, some are a little bit later. So we have a variety of different clients that we work with, like I said, a variety of different viral vector systems. 

 

Jordan Ruggieri 02:08

Anything with cell and gene therapy now makes me so excited. There’re so many cool things that are that are coming through. 

 

Dan Mitchell, PhD 02:31

There's a lot going on. 

 

Jordan Ruggieri 02:32

It's a really, really exciting space I think. Could we for our listeners who are unfamiliar, could you tell us what is a CDMO, and maybe a little bit of the role it plays, CDMOs play, when it comes to developing cell and gene therapies and researching some of the viral vectors?

 

Dan Mitchell, PhD 02:50

Sure. So a CDMO stands for contract development and manufacturing organization. So we have the infrastructure, facilities, instrumentation and expertise to provide, like I stated before, analytical services, process development services, manufacturing services, and then quality, regulatory and release services as well. So you'll see a lot of times, our clients will either be fully set up with their own labs and developing their own products, but others will be more academic in nature, or somewhere in the middle. So we can service a variety of different clients depending on what they need. Those that don't have any of their own infrastructure, or very minimal, we can provide a lot more giving that we have all the services in house. Others that are a lot more self-sufficient and have a lot of the infrastructure themselves we’ll provide services in the areas where they may having gaps, or maybe a little bit of assistance or maybe a little bit more manufacturing capacity. So generally, our clients will develop a product in the lab and generate that it has promising therapeutic effects, but they often lack the capabilities to produce it at large scale, at the purity that's required to be used within the human population.

 

Lisa Crawford 04:11

I'm trying to understand, you know, CDMO and how it kind of how you guys fit into the process, like, even from a logistical standpoint, when you say that you help your clients perform all these things or purify. Are you sending people into their labs to do this? Or are they sending you product and you guys work on it on your end? Like, how do you guys integrate these processes? Because they're so complex, and there's you have to be so careful? 

 

Dan Mitchell, PhD 04:35

It's a good question. And I've seen a variety of different approaches. It really depends on the client, the stage they're in, the phase they're in, how developed their processes, you know, what analytics are in place and things like that. I've seen scenarios where the client will have somewhat of a either an esoteric or a complex system that they want to train you specifically on. So, we can actually send our personnel to their lab to train in their labs with their subject matter experts, right. Alternatively, the reciprocal can happen. We can have what's called a PIPA person implant, where the client will send someone over here to either truly be the person in plant during the manufacturing operations, or somewhere earlier in the process where they'll train our people on things that they've developed in house that they were transferring over.

 

Lisa Crawford 05:26

Wow, so it's like an a la carte situation for everything.

 

Dan Mitchell, PhD 05:29

It really is. Yeah, each program is pretty specific to itself. You know, we try to be very flexible and meet their needs, provide what they need, you know, scientific expertise and, you know, all the way through the manufacturing and release of their material.

 

Jordan Ruggieri 05:44

Is there an element that Matica maybe specializes in, or that you set your part, set yourself apart? What do you, what do you, what do you specialize in?

 

Dan Mitchell, PhD 05:53

One of the primary things that Matica specializes in is our scientific expertise. We have, we have an absolutely excellent team in our process and analytical departments, as well as our quality control and manufacturing teams, in addition to all of our supporting structures, such as, you know, quality assurance, you know, validation, our facilities teams are amazing. So we shine in a lot of areas, but I think our real claim is the scientific expertise. Clients can bring in their programs, and we can provide them with confident scientific skill sets that have been developed over years with our individual people in their previous and current roles here at Matica.

 

Jordan Ruggieri 06:35

I'm going to hop back a little bit into some of the science and AAV, adeno-associated viruses. There is a reason those viruses are used? It comes up a couple times, even in past episodes. But you know, say that versus a lentivirus or even other viruses, right, I mean that deliver some sort of payload? Like, why are those a focus? Or are there considerations between which viruses to utilize in this process?

 

Dan Mitchell, PhD 07:01

Yeah, there most certainly are. AAV has a very broad tropism, like we were saying before, different target cell types, the different AAV serotypes have different preferences for certain different cell types. So it makes AAV a real promising candidate. Another major reason AAV is very promising is that it's not cytopathic. It's not known to cause any disease in human whatsoever. It's truly termed the adeno-associated virus. It was originally discovered as basically some unknown contaminating virus in a lab producing adenovirus. So it's like, what's this small virus that's hanging around. So it is called an adeno-associated virus, until people started learning more and more about it. AAV stands for "almost a virus", because by itself, it, you know, it has doesn't really do anything on its own, so it needs the assistance of what's called a helper virus. Primarily adenovirus, but herpes virus, and among others, can also provide those helper functions to basically boost AAV into producing and replicating itself. So those are some of the primary reasons it's, it's preferred, like I said, it's not toxic or not cytopathic to humans. Another thing is AAVs are endemic in the human population, which means that most people their immune system have encountered AAVs somewhere along their life. So you'll have circulating immunity to them. So that's a consideration for selecting your viral vector, because gene therapy, in effect, is you want to determine and select a vector that's going to have the best chance of surviving long enough to deliver its therapeutic effect so you can kind of perceive it as the opposite mentality of a vaccine, right. A vaccine, you're giving someone a virus, and you want the immune system to see it. You want the immune system to learn what it is, learn how to eradicate and remove it from the system as quick as possible. In gene therapy, you want to evade the immune system for as long as possible. So given that there are so many different AAV serotypes, we can select those that are less endemic in certain populations, or that, you know, certain individuals may not have been exposed to, and then it gives it a longer chance for the to evade the immune system. Ultimately, the immune system will pick it up and eliminate it. But some of the other ways around that would be like we were talking about before, where, you know, you do site-specific administration and things like that.

 

Lisa Crawford 09:35

For someone like me, when you hear virus, you think of one very specific thing, which is introducing something negative to the body, especially with COVID all of that. But when you talk about viral vectors, you're not saying, "Oh, exclusively, we're just introducing diseases into the human body." You're using viruses themselves as a transport vehicle and that's it?

 

Dan Mitchell, PhD 09:56

Pretty much, yeah, so that's the basics of gene therapy, right. So you're basically, you're taking a virus, you're removing the viral material, the viral genome, from the particle itself, and then putting in the gene of interest. With Duchenne muscular dystrophy, the there is a genetic deficiency in the dystrophin gene, right. So it's deficient, either it's truncated or, you know, something like that. So what the viral vector does is it delivers a fully functional variant of that gene to the target cells of interest, and then now the target cell can utilize that gene to generate the dystrophin protein, which will assist in the functionality of the cells.

 

Lisa Crawford 10:42

So not hashtag, not all viruses are terrible, like they have their uses. And in your point, obviously, these are not damaging, like the AAV you were talking about. They're broad. They're not going to cause issues in humans. So we don't necessarily have to think evil when we think virus? 

 

Dan Mitchell, PhD 10:58

Yeah, it's an interesting perspective. And, you know, in the natural setting, you know, the wild type viruses, you know, they have their own, you know, function or purpose, right. Their goal is to just replicate and make more of themselves, right. So, and then that has a negative effect on, on, you know, the host in that case, right. What we do is we modify it. So generally, viruses in nature are not positive, right. So, you know, AAV is an interesting one, because it's, it's just not cytotoxic, not pathogenic at all to humans, right. Everyone in their life has come into contact with AAV somewhere along the way, so the term is seropositive. So you actually take blood samples from subjects and test for antisera against AAVs, and you can say, "Okay, this subject has been come into contact with these different AAV serotypes."

 

 

Jordan Ruggieri 12:00

Taking something bad and turning it good, 

 

Dan Mitchell, PhD 12:03

Pretty much

 

Jordan Ruggieri 12:03

Depending on, depending on the, on the virus that's used.

 

Dan Mitchell, PhD 12:08

Yep, yeah. And it's a real juggling unit, because you like we were talking about before you have to really confirm the safety profile of the ultimate drug product itself, but also the viral vector, right. You want to make sure, and that's what the whole purpose of the clinical trials are, right. They test for safety, and then things like that. So, and then the process impurities that we want to remove, you know, are also, you know, safety related.

 

Jordan Ruggieri 12:35

It's almost like you're taking the UFO and you've stopped the alien from invading Earth, and you've put a human in it to then go explore space.

 

Dan Mitchell, PhD 12:43

Pretty much, yeah, utilize, take the good parts of it and remove the bad parts.

 

Jordan Ruggieri 12:48

Talking a little bit and moving, moving to a different level here, how do you evaluate which technologies to bring into your labs?

 

Dan Mitchell, PhD 12:58

So generally, when you're looking at viral vectors, you want to determine a certain subset of analytics, right. So you want to look at the particle titer. So you want to see how many physical viral particles there are, but that assay itself, or that analytical approach only tells you how many physical viruses you have. It tells you nothing about what's inside them, if it contains the DNA that you want in there, or the RNA, if it's the correct sequence, right, so all it tells you it's a physical particle. So we want a technology that can give that physical particle analysis, but we want technologies that can look at what's inside the viral particle. So you know a digital PCR system, or quantitative PCR system, or, you know, a qRT-PCR, if it's an RNA virus, right. But then there's a variety of other techniques and technologies out there that allow us to look at other characteristics of these vectors. We talked a little bit about aggregation. So there's an instrument that can tell you if things are aggregating. It looks at size distributions. So knowing the size of this AAV in this context, if you see things of multiples of that size, then you say, okay, that's an aggregate of 2, 3, 5. Other characteristics we look at are an empty to full ratio. Sometimes the particles don't carry anything. They're just completely empty, you know, like we talked about, sometimes they carry the correct gene of interest, but other times they may package something else. So, so we can look at those different characteristics, and then we also bring on a technology and the capabilities, the skill sets that allow us to evaluate the virus's potency or capability. So this is often an infectivity assay, so basically applying it to the cells that it would be applied to in the clinical setting and determining the efficacy and the output there. Among some other technologies we have is, you know, flow cytometry, that can help us look at if a cell is transduced by a viral particle that has it expressed a special protein that it didn't normally express. We can take a look at that. So that's more of a more of a potency assay. So those are some examples on the analytical side, and then on the process side, we'll bring on technologies like bioreactors or shake flask systems and things like that to allow us to grow cells at different scales and then to transfect or infect them, and then do the subsequent downstream purification. So we'll have different downstream FPLCs or chromatography skids and things like that, that provide the capability to purify out the vector, purify away the things you don't want and concentrate on the things that you do want.

 

Jordan Ruggieri 15:49

So you mentioned qPCR and digital PCR. We love those technologies here at Absolute Gene-ius. I know you're aware of that. How do you use those in your in your current workflow? And is there a way that you use them differently? 

 

Dan Mitchell, PhD 16:06

Absolutely. So, yeah, primarily we use them to evaluate genetic material, right. So we talked a little bit before about the residual host cell DNA. So if we grow AAVs in, say, 293 cells, after we break open the 293 cells, we no longer want anything from the cells present because that has no therapeutic positive effect. It could potentially have a negative effect because it's a relevant protein load that you might be administering to the subject that might cause a reaction, right. So we want to remove all that. So one of the assays we'll utilize these, these PCR technologies, on, is to do a residual host cell DNA assay, and that will tell us what residual, what remaining, DNA from the host cells, or the cells we grew the virus in, remains in the material. In addition, we use these technologies to do direct characterization assays on the viral vector itself to determine the content of the viral particles and the genomic concentration. And then we can utilize that to compare to a physical particle, to give us an empty-full calculation, physical to genomic. But then we also have technologies to look at directly about at the empty-full characteristics of the material.

 

Jordan Ruggieri 17:25

Between the two technologies. I mean, how do you how do you utilize them in different ways? So for instance, like, are you using qPCR for quantification, where you're maintaining some sort of standard curve? Are you looking at more of like, presence, absence, and then say, like on the digital PCR side is you then go to a different analytical level to try and get some more absolute quantification as you kind of scale? How are they used, kind of, you know, in conjunction with each other?

 

Dan Mitchell, PhD 17:55

Yeah, we'll use either. A lot of times our clients will come to us with a preference. They'll request either the digital platform or they'll request the quantitative platform. And like you mentioned, there is the standard curve for the quantitative platform, so that has considerations you need to take it and take into account. A qPCR assay is often only as good as your standard curve material is. So if you prepare your standard curve well enough where it's a true you know, tenfold between the different standard points, you know, and that's reflected clearly in the CTs, you know, then you got a really good standard curve. Because you're telling the instrument with the standard curve, “This is how much this material is at this point. So if you get this signal, that's how much material.” So if you give it the wrong information to start with, when you later interpolate that data from the standard curve, you're going to get you know information that may not be exact. With the digital platforms, there's no standard curve, right. So it's, as you stated, a more absolute quantification. So it gives the ability to just test the material directly. And then answer your question about, you know, a real qualitative versus quantitative approach, where quantitative would be determining the actual titer or concentration, qualitative would be like you said, you know, “Is it present or not?” often we can apply those, those approaches to your residual replication competent viruses, so as we generate more of the recombinant vector, the opportunity or possibility exists for some genetic recombination event to take place and revert that recombinant vector to a wild type vector. So we'll have tests in place that will look for those wild type virus sequences to determine if they're present or not. And sometimes they can be present at such a low concentration that you really need a refined method to be able to pick them out.

 

Jordan Ruggieri 19:54

Makes a lot of sense as you go through making sure you're not getting things reverting to wild type. And obviously you wanted to have the gene of interest, right, to get in there the correct payload. Very interesting. How, how does sequencing come into play for this? It is also very similar just making sure you have the right, you know, nucleic acids in your vector, and you know there's not that recombinant or any mismatch? Do you use sequence sequencing in that regard, or any other applications that you might utilize it for?

 

Dan Mitchell, PhD 20:26

Yeah, sequencing will be used at a couple different places. It will be used as either confirmation, to confirm that your vector is carrying the exact genetic material and sequence that you're interested in. Alternatively, sequencing can be used to determine if there's any other termed adventitious agents present in your sample, right. So you can basically sequence everything that's in there and then go back to a library and determine to say, “Okay, you know that sequence belongs to, you know, a wild type virus of, you know, adenovirus, or, you know, something that was either introduced somewhere along the way or just may have been present from earlier on.” So, yeah, sequencing would be a more direct evaluation of the sequence itself of the genetic material, whereas the q and digital PCR systems would look at a target amplicon, but it's not actually going to give you any real direct sequence data other than the primers and the probes themselves.

 

Jordan Ruggieri 21:32

Did you know that the QuantStudio Absolute Q dPCR system is powered by microfluidic array plate, or MAP, technology? This technology offers numerous advantages, such as consistent microchamber filling, uniform sample digitization, and efficient analysis of more than 95% of the loaded volume. 

 

Lisa Crawford 21:52

That means when you're looking for a needle in a haystack, you have a 95% chance of finding it, right?

 

 

 

Jordan Ruggieri 21:58

Exactly! The Absolute Q dPCR system and MAP technology also helps provide a low %CV to help generate consistent results. You can learn more at thermofisher.com/map16, that's M-A-P 1-6 or visit the Absolute Gene-ius webpage. The Absolute Q is For Research Use only. Not for use in diagnostic procedures.

 

Lisa Crawford 22:22

And now back to our conversation.

 

Jordan Ruggieri 22:26

Time for Lisa's career corner.

 

Lisa Crawford 22:29

This is my time to shine, because the last life science class I took was senior year of high school. So, but yeah, Dan, I just, what I'm really interested in is hearing your story of how you how you got here. Kind of starting at the beginning, not just, oh, how you ended up at Matica, but what was it that got you into science? Was that something that you were interested in as a kid, did that kind of grow like, how did you even end up in this general field?

 

Dan Mitchell, PhD 22:56

It's, it was an interesting journey. You know, when I was younger, you know, first transitioning from high school to college, you know, I had an interest in, like, marine biology, so then as I started taking courses, I found that as I moved through the academic journey, my focus on life sciences started becoming microscopic and then nanoscopic, right. So it went from animals, right, and marine biology to, you know, bacteria and then viruses. I just kept going with that and then I got my bachelor’s degree in biochemistry, and then I went on to graduate school. And in graduate school, I spent a lot of time learning and existing at that interface between virology and structural biology. And then upon graduating there, I obtained a research associateship through the National Academies of Science. And then when I began, that is where I started really getting interest in viral pathogens and things like that. So I spent about three years in that setting, in the biosafety level four, wearing the positive pressure suit. And then after that associateship ended, I was offered a position, still with the BSL -3, BSL-4 lifestyle. And then after that, I found my way into the biotech space. In 2016. I spent a few years, a little over four years there, and then a short time after that, I was offered the position here at Matica, basically brought me on to build the analytical function here at Matica. So when I joined in 2020 Matica was still very young at that time. And then about a year and a half ago I was asked to step into the quality control as well. So that leads me to where I am now.

 

Lisa Crawford 24:45

Do you miss the pressure suits? Or are you like, okay, I'm glad I've out of that phase of my life, not going to knock a bottle over and cause a problem? 

 

Dan Mitchell, PhD 24:54

It was very interesting. It's very fascinating. I don't want to say I miss it. You know, it was, it required you to be very focused, very hyper acutely aware. You know, you didn't want your air hose attached to at all times. You know, you don't want to knock something over with that or turn and, you know, potentially damage the suit or something like that. So it was very intentional, your motions in the lab.

 

Lisa Crawford 25:17

I run into my dining table once a day, so there's no way I'm going to be allowed in a lab like that, ever. So yeah, in your career progression, I like how you're talking about kind of zooming in more. Do you have any advice for you know younger folks out there who may just be starting or kind of dipping their toe into this area of, you know, what, like if you could go back and tell yourself at that age something that you would want yourself to know, that you could tell them about getting into this field, what would that be? 

 

Dan Mitchell, PhD 25:45

I think, for other younger scientists, I would say, you know, “Just, just don't hold back, you know. And I mean, immerse yourself into it. Don't treat it just like a like coursework where, you know, okay, let me, you know, get the grades and get through it, but challenge yourself to take the work home, you know, and dig a little bit deeper into each chapter and, you know, do some self-study.” But you know, one really good thing, which I didn't mention, which is actually probably really good advice, is try to get to the lab as soon as you can. When I was in undergrad, in my the beginning of my third year, I saw a posting on the wall. It said, “Undergraduate research assistant needed.” So I went and I went to that lab, and she hired me on. It was, you know, 20 hours a week. But it was great because I was in a lab. I was participating with the workload that that lab was generating. And at the time, I was, you know, solely focused on, you know, the coursework and learning what I could, but having that hands on footprint in the lab, in addition to the practical components to the coursework. You know what I mean, being in the actual lab, using the micro pipettors, you know, wearing the lab coat and navigating, placing the orders yourself, you know, because the practical components of the course work, or, you know, they're very high impact, you know, but it doesn't expose you to ordering and why you chose this reagent over that reagent. And you know, it gives you the ability to really learn while you're learning.

 

Lisa Crawford 27:18

So as we all know, a lot of science is failure and setbacks and,

 

Dan Mitchell, PhD 27:24

Absolutely.

 

Lisa Crawford 27:24

Kind of going all in on something and realizing, “Oh, that didn't work.” So what advice or what tactics have you developed over the years to kind of navigate those challenges, because they are such an integral part of the job?

 

Dan Mitchell, PhD 27:39

Patience and thick skin. Yeah. I mean, you're exactly right. I mean, there are, you know, we'll call them like failures, but they're really not right, because every failure gives you the opportunity to say “That didn't work. Let's not repeat that.” 

 

Lisa Crawford 27:54

And that's such an interesting way to frame it. And as a non-scientist, I think we could all benefit from using that framework in our minds, because, you know, in other fields, if you fail, you're like I said, failure is a bad word. Do you recall anything from your entire career where you really feel like it was a proud moment for you? You know, maybe you overcame a lot of challenges, or you had this hypothesis that you're like, "Oh, I'm not sure it's going to pan out" and it did. Just, you know, like something in your career that stands out as a moment where you're like, "This is why I do what I do."

 

Dan Mitchell, PhD 28:28

I don't know of any specific instance, but I think along the way, you know, whether it's having your publications accepted, or getting your grants funded, or getting that job you hoped you get, or, you know, things like that. So I am very thankful of the path that I've had in my journey. You know, I went through some pretty amazing labs had some pretty amazing mentors along the way. So it's, it's been a great journey.

 

Jordan Ruggieri 29:00

Going off of that, is there, is there something that was totally like a low moment for you? Super embarrassing, super embarrassing lab moment? Um. I mean, we've had people talk about things exploding, right. There's something embarrassing that's happened to you that that stands out?

 

Dan Mitchell, PhD 29:20

Nothing that ever exploded, or anything like that.

 

Jordan Ruggieri 29:25

Did you forget to put sample in a plate one time?

 

Dan Mitchell, PhD 29:28

I tend to be very cautious and kind of patient. You know, there have been scenarios you mentioned not putting a sample in, you know, in my earlier days running DNA gels, you know, every now and again you'd run one, obviously, in the real early days, you'd run one, and you'd go to get it and be like, "Oh, wow, is there anything there?" And you literally see nothing. And then you go to your mentor, you know, “What happened?” “You know, did you add stain?” And you're like, "whomp,whomp". So yeah, that's one of those learning moments, you know. And you know, there's other times when, you know, you're sitting in the lab like, you know, wait into the evening, and you're trying to just pour a gel, and it just keeps leaking. And you're, “Why are you leaking?” I just, I just want you to not leak so I can go home and retire. Just never do this again, you know. But what's funny about those, those oversights, is that when the student goes to the mentor and says, “What went wrong?” the mentor immediately says, "Did you add stain?" right. Or “Did you…” you know what I mean? 

 

Lisa Crawford 30:31

Did you turn it off and turn it back on again? Yeah.

 

Dan Mitchell, PhD 30:33

You made that mistake. Okay? 

Jordan Ruggieri 30:35

It happened to the mentor. 

 

Dan Mitchell, PhD 30:36

It happened to the mentor, right. 

 

Jordan Ruggieri 30:38

I mean, my only question, other question is, you know, in your view, what makes a scientist effective in a CDMO environment?

 

Dan Mitchell, PhD 30:49

It depends on where within the CDMO environment. So I'll speak from the AD perspective. So being an experimental scientist is very helpful for analytical development and process development. Being able to say, "Okay, I've tried these different parameters before, many, many times, but now in this setting, I can apply that knowledge to give this the best chance of success the first time." and then it's truly development, right. There's multiple iterations. We go through it a couple times and get it to the point where it needs to be, right. So having that kind of experimental mentality, you know, is very beneficial. But in addition, you know, that that patience. But also the willingness and the resourcefulness to be able to, you know, either dig through a primary literature you know, for what's been published and what's worked and hasn't worked in the past, or to be able to find a technique or technology or reagent that's commercially available you know that that may work for what you're doing. So just having that kind of background and that inquisitive nature, I think, is really essential for the development side of the house.

 

Jordan Ruggieri 31:58

Dan, it was great having you on this episode of Absolute Gene-ius. Very, very interesting. Really cool to hear more about cell and gene therapies and that space. Thank you so much for your time and for your in-depth answers. We really appreciate it.

 

Lisa Crawford 32:13

Yes, thank you so much.

 

Dan Mitchell, PhD 32:15

Yeah, thank you, Lisa. Thank you, Jordan. I was very happy to be part of your show.

 

Lisa Crawford 32:20

That was Dan Mitchell, head of analytical development and quality control at Matica Biotechnology in College Station, Texas. This episode of Absolute Gene-ius was produced by Sarah Briganti, Matt Ferris, and Matthew Stock. We've got more great conversations around the corner in upcoming episodes, so stay curious and we'll see you next time.

 

Jordan Ruggieri 32:38

Hey, Lisa, are we, are we linked? Because I feel a strong co-host bond forming.

 

Lisa Crawford 32:45

I wish you could hear eye rolls.