CRISPR, Then and Now: A 2025 Update with Rodolphe Barrangou

Genome editing pioneer Dr. Rodolphe Barrangou returns to AgTech 360 to share how CRISPR has advanced and expanded since his last appearance in 2021, transforming from a breakthrough technology into a global force across medicine, agriculture, and beyond. From scientific breakthroughs to real-world applications, he highlights how genome editing is reshaping food systems, farming, and human health. Rodolphe shares insights on the FDA approval of CRISPR-based therapies, the rise of gene-edited crops in global markets, and the growing role of AI in designing precision edits. He also reflects on the progress of regulatory frameworks, the importance of public trust, and what scientists, companies, and governments must consider as CRISPR scales from the lab to the marketplace. 

Transcript

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Adrian Percy:

Welcome back to you, AgTech360. Today, I'm thrilled to welcome our first ever repeat guest on the show, Dr. Rodolphe Barrangou. Rodolphe is a distinguished professor here at NC State University and one of the world's leading experts in CRISPR and genome editing. Now, over the course of his career, Rodolphe's groundbreaking contributions to science and innovation have earned him numerous accolades, including induction into the National Academy of Sciences, the National Academy of Engineering, the National Academy of Inventors, and the National Inventors Hall of Fame. Last time we did an episode was back in 2021, which seems a long time ago now, so I'm eager to hear how things have progressed both in your life but also in the world of CRISPR technology. So first, let's talk about you. Give us a bit of an update. What have you been up to professionally over the past four years? Are there new projects, companies, milestones that you've achieved that you want to share with us?

Rodolphe Barrangou:

Well, Adrian, thank you for having me. It's great to be here again, and it's hard to believe it's been since 2021. Four years in CRISPR years, well, being like 20 years in regular life years. So a lot has happened since then in the CRISPR Field. Across the board, the science and the technology have advanced substantially. We have a great toolbox right now that allows virtually all scientists on planet Earth who are average at DNA and genome editing to do anything they can do and anything they want to do, and we've seen tremendous progress in food, in ag, in forestry, and, first and foremost, human therapeutics. So it's a great, great time for CRISPR. And in some ways, I think 10 years into CRISPR technology, we're at the end of the beginning, and it's an exciting time and moment for us. But we're ushering in, I think, the next stage of deploying CRISPR technologies at scale in the clinic, in the field, and in the forest.

As far as I'm concerned, I think we have focused substantially the last couple of years on advancing CRISPR to breed trees, and we actually published a nice paper in Science 18 months ago showing how the combination of CRISPR and genome editing and AI and synthetic biology allows us to now go after more complex traits with multiplexible genome-editing modalities that are efficient enough to target multiple edits at the same time in one species and then change, for instance, lignin content and fiber composition in trees to make forestry as an industry more sustainable. That's very, very exciting.

And then importantly, we've been able the last couple of years to not just focus on the science, but also plant some trees in the greenhouse, plant some trees in the field, we'll talk about that later, and then advance that translationally. So not just the fundamental aspects of CRISPR, but the transformational, impactful, translational aspect as well.

Adrian Percy:

So one of the things I recall in our conversation back in '21 was us making the observation that a teenager can do a CRISPR experiment in their bedroom if they wish. And I think that was true then, it's true now, but that's only part of the story, right? It's moving from, as you are kind of implying, from doing that actual edit until you translate it into some kind of product. And I guess that perhaps is one of the areas that has really advanced over the past four or five years.

Rodolphe Barrangou:

Absolutely. So the idea that the average person can do an average edit in an average species in their kitchen, in their garage, in their high school lab is certainly a reality. You can buy a kit online to do CRISPR genome editing at scale to some extent and affordably, and it can be done, and people are doing it. What's exciting about the field right now is that we are really making substantial progress to translate and apply that great science and that great technology to address the grand challenges that we have before us.

So the therapeutic front, we now live in a post-FDA-approval world. Casgevy, a short while back, was approved as the first ever CRISPR drug to treat sickle cell in patients, endorsed by the FDA, a time when FDA is having challenges, obviously, of all the reasons that we know contextually. But also at a time when people have launched CRISPR-based edited products in the ag world as well. And we're seeing not just the science move along, but the regulations move along, the companies move along and make investments and move that forward and commercialize it, and that's very exciting.

Adrian Percy:

Can we just go back a step? Probably no one else in the world or very few other people in the world can probably explain CRISPR in a very simple and digestible way. We have people that listen that aren't necessarily scientists or haven't heard other episodes that we've done around CRISPR and genome editing. Can you just tell us quickly what is it from a scientific perspective and how would you describe it?

Rodolphe Barrangou:

So CRISPR technically is an acronym that stands for Clustered Regularly Interspatial Palindromic Repeats, which is a mouthful, but it's very descriptive. And in nature, it's a very peculiar genetic element that occurs in about half of all bacteria on planet Earth, including the bacteria in our body, in our mouth, in our various cavities, in our skin, that provides adaptive immunity in those bacteria against invasive genetic elements like viruses. And in nature, CRISPR as an immune system, allows bacteria to cut invasive viral DNA and build phage resistance, for example. That's the science behind it.

What's really interesting about CRISPR is not just the science as much as CRISPR tech or CRISPR technology for genome editing, and what people have been able to achieve, remarkably, almost unexpectedly and in an innovative disruptive manner, is that we can use CRISPR elements and program them as molecular scalpels to cut DNA virtually in any species on planet Earth, and programmably cut DNA at a precise location in a genetic sequence, a CTRL-F in your Word document, and then edit the genome precisely at the side of cleavage.

So we now have a molecular scalpel, CRISPR is a molecular scalpel, that allows people to go into the code of life and rewrite the DNA code, which means we can take genes out, correct broken genes, we can remove or add or change genes. And as a matter of fact, we now have a CRISPR toolbox that allows us to change the text, but also the punctuation. We can change transcription, turn DNA transcription on or off, up or down, and also change the epigenetic state of DNA. That means that virtually we can do anything we want, do any DNA we want any way we want in any species on planet Earth.

Adrian Percy:

And then maybe just walk us through an example of what goes beyond making the edit itself. If you're working in the forestry area, you're transforming a poplar or eucalyptus tree, whatever it may be. From that initial gene edit, what is the process then to actually produce a tree where that gene edit is translated throughout the entire genetic code of that particular tree?

Rodolphe Barrangou:

It is a process that takes a lot of time, a lot of energy, a lot of knowledge, a lot of expertise, and a lot of scale and resources. So in the case of forestry, we would take the best clone that makes the best wood that turns into the best paper in the best forest on planet Earth. So think of a eucalyptus tree growing in Chile or Brazil, we would take that elite clone and then, out of that, take stem cells of trees. And then we would deliver CRISPR into those tree stem cells that are programmed to target genes that we want to change.

And as a matter of fact, for the traits we're working on, like lowering lignin content and changing lignin composition, we need to do five or six edits at least. So we'd go in, deliver five or six different "doses" of CRISPR into some of those "cells," let CRISPR do his job, cut the DNA, repair the DNA with sequence changes that we can then screen, and then we would sequence a bunch of derivative material thereof in different cells and then pick the cells that have the changes that we want in the combination that we want and select those.

And then we have to grow them. We have to induce shoots and roots and regenerate plants in the lab like plantlets, small trees, that can then grow and be healthy and then eventually let them grow in the lab and then take them into the greenhouse. And then maybe after a year or two of greenhouse data, we would put them in a field trial. After two to five years of field trial, we'll put them in the field. And then we go from planting one tree from one cell to 100 trees to 1,000 trees to 100,000 trees to eventually maybe hundreds of thousands of hectares at scale.

So that scalability in space and time is just hard to fathom when you think about it. As a microbiologist, to scale that up with viruses and bacteria, it's very easy in a lab setting, but to have the physical space in a lab, let alone in a greenhouse, let alone in a field, eventually let alone in a forest, if people can think of some of those forestry companies managing over one million hectares of forest at any point in time. It's bigger than some states in the US. So the scalability aspect in space and also the scalability aspect in time is mesmerizing but concerning at the same time.

And some of the projects we're working on, to give you an idea, are going to materialize in the 2040s, right? Because at the time it takes to do it in the lab, a couple of years doing the greenhouse, a couple of years doing a field trial, two to five years, and then a tree rotation that may need 16 years. So we're looking at some of the work that we're doing right now that will pan out in 2048.

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Adrian Percy:

Which is incredible. And thank you for explaining that, because perhaps forestry is on one end of the extreme because of obvious time it takes to grow trees to maturity. But I think some people will think, "Okay, these gene edits, you can do it overnight in a lab or over the day in the lab," and not understand the implications of how the scaling effect really needs to take shape, and so thanks for explaining that.

Coming back to some of those other examples, you mentioned FDA-approved drugs. I noticed that FDA had recently approved a gene edit in pigs, so it is definitely coming to food, into agriculture. Where else are you seeing CRISPR now operating at scale and products actually getting out into the public domain and actually being very impactful in whatever application we're talking about?

Rodolphe Barrangou:

Yeah, I'm going to give maybe two examples. So one in therapeutics. The FDA first approved Casgevy as a cell therapy for sickle cell, and that was remarkable. In this case, it's an ex vivo therapy. So we take cells out of people, we edit them in the lab, and then infuse them back. Blood delivery is fairly straightforward, not trivial, but straightforward. That was the result of 10 years of hard work by a lot of people, and that ushered in a whole new era for gene therapies and cell therapies in medicine, because that engineering ability can now be deployed at speed and at scale to develop drugs. And those patients, some of those patient populations are large. We're talking about hundreds of thousands of people or millions of people.

And it's hard to do, it's expensive to do. Some of those gene therapies are in excess of $1 million per dose. It is a single dose, so you only need one time, and you save a life. So over the course of the patient and the lifetime of the patient, $1+ million sounds like a lot of money, but it is worthy of a human life. And once we get that price down, 10X will be where we need to be to scale that up. So the scalability is not financial as much as is the cost of making it.

Adrian Percy:

And is there a path to reducing that cost?

Rodolphe Barrangou:

Absolutely. So there's a lot of people very hard at work that are not just working on the engineering or the sales themselves and the engineering or the drugs themselves, but engineering the scalability of the manufacturing. A lot of that cost also comes from the regulatory process inherent to developing the drugs, right? Oftentimes, people use the magic number if it cost $1 billion in 10 years for a drug to materialize. And if you cut that substantially, because CRISPR as a modality, you only change one piece of CRISPR to develop the next CRISPR drug, once the manufacturer has shown they can do it, they can do it safely, they can do it responsibly, they can do it scalably, and they can generate a safe and efficacious drug that is FDA-worthy, the hope is that the path forward for that company to develop the next drug would not require the same amount of investment. And if you can cut down on the regulatory cost, you're going to cut down on the sales cost and the operational cost. So there's a path forward for that.

And then also right now, there's a lot of work in N-of-1 studies where you have the magic one customized extreme personalized medicine drug where the one drug will be designed for one patient that has the one mutation. So we'll maybe look at there in a subsequent question. If you take the other part of the equation and put therapeutics aside, and it's great to save lives and develop great medicines and therapeutics for patients who need them, I'm actually quite excited about the tremendous progress we've made in the agricultural world. And one of the reasons is not just the potential of the technology to breed scalable and more sustainable crops and plants. You think about the scale of corn and soy and rice and wheat and all the great plants that a breeder has spent a lot of time breeding by editing today to address yield gains, but also changes in environment, drought conditions and pests and disease and whatnot.

We tend to benefit substantially from that in terms of farming, and the projection is that by the end of 2030, maybe 100 million farms will have planted a CRISPR-edited seed. What excites me the most, as a matter of fact, is the number of people who stand to benefit from that work. And when you look at the impact of agriculture on us as a species, the whole world stands to benefit from that. And there's a lot of scientists, there's a lot of industry, there's a lot of governments who have recognized that opportunity, even regulators that have anticipated that potential, that have been very hard at work in the last four years to collaboratively work together to usher in the next era of agricultural miracles and bring CRISPR to the field.

And in North America, in South America, in Africa, in Southeast Asia, there's been a large array of diversified crops planted in the field that has shown real commercial potential, to the point when we are already seeing commercial launches of the products, like the CRISPR-edited tomato in Japan and the CRISPR-edited tomato in the UK. Of course, CRISPR-edited corn. Of course, CRISPR-edited soy. For us here in North Carolina, we have Pairwise Plants, whose mustard greens commercially launched and whatnot. There's a whole pipeline of CRISPR-edited fruits and vegetables and plants and crops that will be next.

Adrian Percy:

So you said, "Everyone stands to benefit." So let's just dive down into two groups. So how will consumers benefit from CRISPR technology? And then let's talk about how farmers might benefit.

Rodolphe Barrangou:

Consumers will get extensive access to a more biodiversified food supply chain that is more affordable, because the farming process will be more sustainable. So we're going to have a more diversified food supply chain, we're going to have a more diversified bio-based food optionality, and those foods will be made more affordably and scalably and sustainably, because we can breed in traits that allows those diverse crops to be more resilient and resistant in a changing environment.

Also, people probably don't realize how hard it is to breed a species. By bringing CRISPR to non-clinical, non-model species, people will get access to more local crops. So we're going to see a diversification beyond corn, beyond soy, beyond rice, beyond wheat where people can use and consume, local yams, local sweet potatoes. We're going to be able to breed bananas that are more diversified and tasty. We're going to go to the citrus industry and make it more tasty and wholesome, and we're going to be able to have coffee for longer, and we're going to have to have maybe better wine, a more sustainable wine for a longer period of time.

So I think people haven't realized as of yet that by the scalable breeding potential of bringing CRISPR to crops within breeding programs, we're going to be able to breed everything better, everything more affordably, leverage what nature affords us in the most diversified way possible and have continued, sustained, longer-term, more accessible access to much more diversified, tastier and nutritious food.

Adrian Percy:

With obvious benefits for farmers and farming communities who are producing those different products.

Rodolphe Barrangou:

Exactly. So between the breeding process and then the consumer consumption, eating the food process, the farmers have to make it happen. And what's very compelling for farmers is they're going to have some substantial gains in terms of yield. They're going to have even perhaps more substantial gains in terms of the efficiency of their farm. They're not going to have to apply as much pesticides or insecticides or herbicides because we can bring that in, and then they will be able to manage the volatility of the weather more efficiently. So we'll be able to breed-in better and faster drought tolerance or frost tolerance, and we know that the pace and scale of which the weather is changing is both concerning and unpredictable, and being able to use the best toolbox in the world to account for that preemptively is going to revolutionize farming. It's like the next revolution of farming, so to speak.

And I think farmers are going to stand to benefit so much more from CRISPR than they realize right now because we're going to have much better seeds, and we're going to be able to customize the seeds more precisely to different environments and different conditions. If we can tell when the season's going to be warmer, we can do that faster. If it's a season where there's going to be more pests, there's certain kinds of pests, we can do that faster. And over the long term, rather than have to move the farms to the right environments, we're going to have to keep the farms that we have right now and extend their longevity and extend their potential and extend their legacy.

And for people who understand the concept of terroir, for example, I don't want my Bordeaux to be grown in northern France let alone Belgium. You don't want your Chianti wine from Italy to have to move to Switzerland. You don't want your wheat from Germany to move up to Denmark. So I think some of the historical cultural value that we spent thousands of years to develop in our food supply chain, our food systems is going to be there for longer. And people haven't realized that as of yet, but they will, sooner than later.

Adrian Percy:

So one of the things that you have put a lot of effort into I know is regulatory and societal acceptance of CRISPR and CRISPR products. So where are we? You're describing now the fact that actually these products are on the market in many places around the world, that we are consuming them. There's not been a huge backlash that I'm aware of. But where are we in terms of that societal acceptance and how is the regulatory system catching up with the technology at this point in time?

Rodolphe Barrangou:

It has been mesmerizing to me, because I always thought science was going to be the hard part, right? And science is hard in and of itself, and genome editing is hard in and of itself, but surprisingly, and to some extent perplexingly, it's been interesting to me to realize the responsibility that we have as scientists to help our stakeholders who don't know the science, who don't understand the science, who are not familiar with the technology to make science-informed decisions. I think we appreciate today how hard it is sometimes for the public to appreciate science and make science-informed decisions, but this conundrum actually applies to regulators and governmental agencies, because sometimes science evolves at such a fast pace that there's a gap and a delay between the time a technology is developed and the time a technology is implemented commercially and then has to be commercialized and regulated accordingly.

And many of my colleagues have invested some of our time and resources to help educate regulatory agencies so they can have science-informed policies and frameworks that adapt themselves to the changes in technology. We've been very successful originally in the US, and I've been impressed, if not to some extent surprised, by the speed and scale at which regulatory agencies throughout the world have caught up. So South America has really to get a lot of credit for educating themselves very early on in the ag world. And as a matter of fact, I think we can make the statement that the most diversified genome-editing crops trials are underway in South America right now.

Likewise, I think the Bill and Melinda Gates Foundation and other people in academia have done a great job at informing and educating specific countries in Africa that have recognized the potential of genome editing to grow their own crops locally, and I think we are now at six different countries in Africa that have changed their framework just in the past year or year-and-a-half to adapt to this, and there's a whole long series of countries that are going to come up next in that part of the world.

And then I am pleased and encouraged by the fact that the trial log in the EU is moving along, and there are some reasons to be hopeful that by the end of the calendar year, we may be in a world where the EU regulatory framework has reached the expected and anticipated milestone of enabling genome-editing crops. Now, of course, EU is within Europe, and it's important to point out that there are parts of Europe that are not in the EU, like the UK, who have recognized, strategically, economically, financially and scientifically, the potential of that technology and have taken great proactive efforts and endeavors as a Minister of Agriculture and as a nation to incubate a whole ecosystem to promote the deployment of genome editing in agriculture. And I think that's a great template for others to use, and I commend the UK for leading the effort in the continent of Europe on that front.

Adrian Percy:

Let's look to the future. You're kind of talking about how the regulatory system is almost there, at least in agriculture, which is exciting to hear. We see a lot of companies. You referenced a couple of companies locally here in North Carolina, but we know that other companies across the planet that are deploying now this technology, big and small companies. We're seeing a lot of scientists intrigued and interested in exploiting these tools. So what advice are you giving to scientists and companies that see CRISPR as an opportunity? What are the lookouts for them and what would you have them focus on?

Rodolphe Barrangou:

Yeah. So it is an interesting question. There's a couple of things that are relevant here. Some are technical. So technically, the CRISPR's part for cutting DNA is almost straightforward now, but there's still a lot of insights that we need to develop into understanding what to target and what gene, as a matter of fact, what genes plural, because some of those traits require the involvement of multiple gene sequences. So how can we better inform our genome-editing strategy by amassing, analyzing large amounts of genetic data to figure out when to change or tweak a particular trait, what are all the genes we need to change? And then once you know all the genes you need to change, you need to know what edits you actually want to generate. Are they knockouts? Are they deletions? Are they indels? Are they allele replacements? Or do you need to tinker with the promoter to change and modulate the expression level either up or down?

So I think right now, a lot of the pioneering companies, like Inari Ag and others, are really understanding that challenge and are really putting in the right resources to not just do CRISPR in terms of editing modalities, but use AI and machine learning and analytics to predict what combination of genes you need to work on to get the traits that you want. I think in academia, there's a lot of people working on the challenges of delivery. So being able to deliver the genome-editing machinery into an elite germplasm of interest is not trivial. It's hard in corn, it's hard in soy, but we've been doing this for a long time. But when we do that in carrots, when we do that in yams, we do the sweet potatoes, we do that in peanuts, there's no protocol for that readily available. So having the wisdom to recognize that the technical hurdles to get there is important.

And then also I think, from a strategic standpoint for companies, it's knowing what traits and what crops to prioritize in what geographies for what customer bases. So we see some people prioritize large-scale row crops. And the big guys in the world, whether we're talking about Bayer or Corteva or BSF or Syngenta [inaudible 00:28:37] China, they know what crops they want to work on, they have the elite germplasm, they have the genetic insights, and now, it's deploying that at scale. Other people, like Pairwise, they're going to have to work through what does it take to deliver gene-editing modalities to berries? You want to do that in avocados or cherries. What protocols do we have? And having the courage and the wisdom to invest in technology development to be able to do hard things in hard species that we don't know a lot about matters.

I think in other cases, it's going to be people have the wisdom to collaborate and transcend the boundaries between government investments, not-profit investments, industry investments, and academic investments. And that's why parts of the world. Like Africa, I'm so impressed with the Bill and Melinda Gates Foundation investment and commitment to working and convening and compelling all the stakeholders to work together, to work on the right crops, the right way, at the right time with the right regulations and the right tools and the right people, because unless you have local endorsement by the farmers, it's not going to work. And long story short, you have to have the wisdom to recognize you need to adapt your playbook to almost every single case on a contextual basis. You have a geographical aspect, you have a plant-genetics aspect, you have a genome-editing aspect, you have a commercial-opportunity aspect. Of course, we could talk about IP, of course, we could talk about regulations, and of course, we can talk about the science, but I think the hard part is to assemble all the pieces of the puzzle you need to be successful on a case-by-case basis.

Adrian Percy:

Rodolphe, thank you so much for joining us again and sharing your insights on how genome editing continues to evolve and impact the world around us. And it's really fascinating to hear how experts like yourself can blend this mixture of science, technology, entrepreneurship to drive really transformational change in this particular area. So thank you.

To our listeners, if you enjoyed this episode, be sure to follow and subscribe to AgTech360 on your favorite streaming platform, so you never miss an episode. Thanks, again.

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