The CRISPR Craze


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2022 marks the 10th anniversary of a remarkable report that paved the way for the CRISPR gene editing revolution. The senior authors of that study – Jennifer Doudna and Emmanuelle Charpentier – shared the Nobel Prize in Chemistry in 2020 for developing the “genetic scissors” that has already been deployed in the clinic, curing a handful of patients with sickle-cell disease. But for all of its early success and promise, CRISPR has also been at the center of a major controversy. In 2018, gene-edited twin girls were born in China, which triggered an international firestorm.

Kevin Davies PhD, executive editor of The CRISPR Journal, has followed all the twists and turns in the CRISPR saga for his book Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing, which was published (as it on cue) one day before the Nobel Prize announcement. In this talk, he’ll shine a light on the “heroes” of CRISPR who developed the genetic scissors; highlight progress in precision genome engineering for genetic diseases; dig into the ethical controversies and preview some exciting new avenues for the field.


Kevin Davies, PhD
Author
EDITING HUMANITY: The CRISPR Revolution and the New Era of Genome Editing

 

TRANSCRIPT

Alessia Ortega:

Hello and welcome everyone to today’s S3 webinar, the CRISPR Craze. My name is Alessia, and I will be your host for today. And the speaker for today’s presentation is Dr. Kevin Davies. He’s the Executive Editor of the CRISPR Journal and the Author of Editing Humanity, the CRISPR Revolution, and the New Era of Genome Editing.

Alessia Ortega:

So thank you all so much for joining us today. He is going to shine light on the heroes of CRISPR who developed genetic scissors. He’s going to highlight the progress in precision genome engineering for genetic diseases, and he’ll dig into ethical controversies and preview some exciting new avenues for the field.

Alessia Ortega:

Everyone joining today is going to receive a complimentary copy of his book, Editing Humanity. And one more thing, if you’re joining us, you can submit any questions that you have using the Q&A button at the bottom of your screen. We will be having a Q&A portion at the end of the webinar. So please submit any questions that you want to be asked to Dr. Kevin Davies using that Q&A button. Now without further ado, let’s get to today’s presentation.

Dr. Kevin Davies:

Thank you very much, Alessia, for that lovely introduction, and you’ve beautifully highlighted the four main themes that I would like to tackle in today’s book. In today’s talk, I really to thank Sanguine for their generous hospitality, not only in hosting this presentation but in offering to deliver books to everybody who’s attending. I’m really thrilled about that.

Dr. Kevin Davies:

So the CRISPR Craze is the title of the webinar, and like many of you, I first began picking up on the buzz about CRISPR from the mainstream media. I kind of missed the early major scientific presentations and discoveries; I was doing other kinds of publishing at the time. But right about 2014, ’15, ’16, there was just no escaping this new gene-editing technology that just seemed to be sweeping the world by storm.

Dr. Kevin Davies:

Almost overnight, it was suddenly appearing on every major magazine cover, it seemed. Then 60 Minutes was covering the story. Here is Bill Whitaker, the 60 Minutes correspondent interviewing Feng Zhang, one of the leading scientists in the field at the Broad Institute. This was a redo because they originally filmed this with one of the other presenters who’d been sacked. So Bill had to, had to step in for a repeat performance.

Dr. Kevin Davies:

Then we had CRISPR landing at the movie Plex taking on Dwayne Johnson, Johnson coming out on top, obviously, as he always does in these kinds of movies that was rampage. And in 2019, CRISPR popped up on Jeopardy. I think for the first time with this question, Jennifer Doudna and Emmanuelle Charpentier are co-inventors, Jeopardy, announced of the revolutionary tool CRISPR. You can answer that to question in the privacy of your own home or office.

Dr. Kevin Davies:

I think the producers of Jeopardy were onto something because it was less than a year later that Doudna and Charpentier shared the 2020 Nobel Prize for chemistry for the discovery of a method for genome editing. And I think the press release actually used the term genetic scissors, which is a handy way to think about what CRISPR technology can do.

Dr. Kevin Davies:

These are two lovely, charming photos of the winners receiving their gold medals not in the usual surroundings in Stockholm at a Royal Gala. But a makeshift arrangements had to be made, of course, because of the pandemic. So Charpentier received her prize and medal in the Swedish embassy in Berlin, and Doudna received hers literally in her backyard in Berkeley, California. So that was nice.

Dr. Kevin Davies:

It’s been a remarkable ride for CRISPR. The first description of this strange phenomenon goes back to the late 1980s. It had nothing to do with gene editing. Here were a small group of Japanese microbiologists sequencing the DNA of a bacteria and stumbling on a strange, mysterious repeating pattern of sequence motifs. And obviously trying to figure out, well, that’s weird that doesn’t usually crop up by accident. There must be some sort of purpose or some function to this strange sequence. What could it be? The scientists in question were actually more concerned with the genes nearby, so they didn’t even stop to investigate further, but others became intrigued and interested, and you can think of this what this diagram shows. I’m not going to go too heavy into the science, but here’s a familiar sort of DNA sequence trace showing the four letters of the genetic codes, A, C, T, and G, in different colors.

Dr. Kevin Davies:

You can think of this CRISPR array as a clustered set of repeats. One way to think of it is almost like the DNA equivalent of a pop song. Pop songs are usually composed of alternating versions of chorus and verses, and usually, the verses are naggingly identical to each other. But in this case, we have the pink repeats that are the choruses that are identical to each other, but the white sequences in between the repeats are completely unique. They bend no resemblance to each other or, indeed, at the time to anything else in the database.

Dr. Kevin Davies:

So a small, steadily growing group of microbiologists became really fixated on trying to figure out what was this CRISPR set of sequences doing? What was their function? And in 2017, I become completely bowled by CRISPR, totally fixated on it, and decided not only to write a book about the subject but also to launch a journal on CRISPR. And that became the CRISPR Journal launched in 2018.

Dr. Kevin Davies:

It gave me the luxury and the opportunity to travel to various destinations and visit and interview some of the leaders in the field, including this gentlemen Francisco Mojica, who works at the University of Alicante in Southeast Spain, a beautiful tourist destination. And he was doing a lot of his work here at the salt lakes of Santa Pola, just south of Alicante. And he took me there on my obligatory visit to meet him. And he explained that he was studying the bacteria that thrive in these salt, these lagoons, these salt lakes, where they’re literally crystallizing salt out of the Mediterranean. He felt earlier in his career that CRISPR must be encoding proteins that have some basis in allowing the bacteria to thrive in these particularly harsh environments. These very salty environments.

Dr. Kevin Davies:

It was a lovely theory. It was totally wrong, but Mojica could not stop thinking about this particular genetic sequence. He coined the term CRISPR in 2001. This is the email he exchange with a Dutch scientist who ironically left the field because he couldn’t get funding. This was such a backwater at the time, just 20 years ago, but Mojica stubbornly persisted, kept running bioinformatic searches of these unique sequences between the repeats in the CRISPR array until one sunny afternoon he hit Pedro at science journalists are fond of saying where he found a match to a viral sequence. So in the picture that suddenly kind of crystallized that what bacteria were doing was capturing short snippets of viral DNA and stitching those sequences into their genome, almost like filing a mugshot into a filing cabinet and the experimental proof of behind theory proposed theories proposed by Mojica and others was that this was part of an immune defense system.

Dr. Kevin Davies:

This came just a couple of years later, in 2007, in a landmark paper in science with a group led by Rodolphe Barrangou, who I have the pleasure of working with at the CRISPR Journal. He’s a professor at North Carolina State University. But at the time was working in industry for a yogurt company, and they proved that for their dairy cultures to be successful, they had to manipulate the CRISPR system so that the bacteria in their starter cultures had this immune protection, this genetically encoded immune protection against specific viruses that would otherwise completely turn the cultures to mush. And this is important because, as any pizza-loving fan will know, this is how your pizza cheese and many other products are made. This is obviously high industry steaks, and CRISPR is used to build these start packs that you can buy from many leading companies.

Dr. Kevin Davies:

So here’s now the new look biology textbook because none of this was known barely 15 years ago. This is the CRISPR mechanism. We’re still not talking about gene editing. That’s about to be the next stage of the story, but here is a virus depositing or being attacked by part of the bacteria’s defense machinery; bits of DNA are stitched into the genome, into this CRISPR array. And then, those sequences can be reactivated, expressed, and coupled with the scissors. The scissor part of the genetic scissor is a protein, a nuclease that cuts DNA called a Cas protein. And by coupling the Cas protein with one of these sequences that provides the programmability, the targeting mechanism that tells the Cas enzyme to cut this only, this viral, encoded DNA and not any of the bacterial host DNA, hence the specificity.

Dr. Kevin Davies:

So for about five years, from 2007 to about 2012, investigators were busy teasing apart the molecular basis of this and trying to understand this mechanism better. And this is the team that really won most of the plaudits and made the big breakthrough in 2012. Here’s Jennifer Doudna from the University of California, who agreed to team up with Emmanuelle Charpentier, a French microbiologist. They met in Puerto Rico at a conference in 2011. They got on well, they hit it off, they agreed to form a trans-Atlantic collaboration with Martin Jinek in Doudna’s group and Krzysztof Chylinski, a grad student in Emmanuelle’s group leading the collaboration, and that collaboration culminated in a landmark paper published in science in the summer of 2012, a programmable dual RNA guided DNA and nuclease in adaptive bacterial immunity.

Dr. Kevin Davies:

Now during my research for the book, I obviously got to meet sort of the heroes of CRISPR, and two years before the Nobel Prize, the biggest prize up to that point for work in the CRISPR field was the Kavli Prize presented in Oslo rather than Stockholm. It is a biennial prize, a very prestigious prize in its own right, and here are the three winners for the invention of CRISPR Cas9, a precise nanotool for editing DNA. You see the features of Charpentier peeking around the King of Norway and Doudna, of course, but there’s a third person on stage.

Dr. Kevin Davies:

This is Virginijus Siksnys from Lithuania, who was working independently of Doudna and Charpentier. He published a paper that same year, but he might have scooped down on Charpentier to a degree, but the journal that he submitted his paper to initially rejected it and decided not even to send it for peer review. So he was sort of like snakes in that as he was sent to the back to the first lane of the game board and had to start all over again. By the time he published, this paper had already come out, and so many people kind of ignored it and just assumed he’d been scooped.

Dr. Kevin Davies:

He also didn’t have one of the key elements of the Doudna Charpentier paper in reducing CRISPR to its most simplest components by taking two different RNAs that are required in the mechanism to target and cut DNA and stitch them together into what’s called a single guide RNA. So that was a very important part of that paper.

Dr. Kevin Davies:

Now the Doudna Charpentier paper was important, but they were missing one big thing, which was, they weren’t yet able to show that CRISPR could work inside human cells. That was a big open question because this is a bacterial system for knocking off viral DNA. So does that mean it would work in the very different environment of a human cell nucleus? Well, many groups set out to prove whether it could or couldn’t, and the first team to demonstrate that it could was led by Feng Zhang at the Broad Institute. He submitted his paper to science three months after the Doudna and Charpentier paper came out, and it was published in the very early part of 2013. In the same issue as a similar study, an independently performed study by this scientist who many of you recognize this is George Church from Harvard Medical School.

Dr. Kevin Davies:

So suddenly, in January 2013, two groups have proved that CRISPR can work, gene editing can work in human cells. And that was a very important step toward the idea that CRISPR could be a clinical or therapeutic gene-editing tool. And I love to show this a little kind of time lapses video from a Japanese group kindly shared by them. And this shows CRISPR in action. The yellow blob is Cas9, the main nuclease that is used in CRISPR systems, although there are many others, and here you see it’s sitting on a strand of DNA, pausing, thinking about it, and then eventually cutting the DNA. And from this point on, the cell can either repair those two frayed fragments of DNA, or you can supply an exogenous piece of DNA that you would like to stitch in and therefore edit the sequence that you’ve targeted in this fashion.

Dr. Kevin Davies:

So, as I said, with the demonstration that CRISPR could work in the context of a human cell nucleus and in the human genome and have the specificity to find the gene that you are targeting, not just in a tiny bacterial single chromosome, but in the vast 23 pairs of chromosomes and thousands of times millions of times, bigger genome in a human than in a bacterium this launched a biotech revolution.

Dr. Kevin Davies:

Many of the names on this slide are companies that you are familiar with. The ones above the line are publicly traded. The ones below to my knowledge, not yet public but could well be going public at some point in the next year or two if the markets allow, and several of these companies have already launched clinical trials, which in the space of 10 years from that proof of principle study is remarkable.

Dr. Kevin Davies:

I know that Sanguine, the host for today’s webinar, have deep interests in sickle cell disease. So it is wonderful to report that sickle cell is really the area where we’ve seen the most progress so far in the clinical application of CRISPR genome editing. Now this work is work that has been published in the New England Journal of Medicine in late 2020. It is work from CRISPR Therapeutics, one of those publicly traded biotech companies now in partnership with Vertex Pharmaceuticals, and Vertex is now leading this collaboration.

Dr. Kevin Davies:

Victoria Gray is one of the first patients in this trial who has to talk about her experience. She’s been widely profiled in an ongoing series on national public radio hosted by Rob Stein, science correspondent for NPR, and the results of Victoria’s treatment and of many of the other patients in this initial trial have been nothing short of spectacular.

Dr. Kevin Davies:

As many of you know, sickle cell is a devastating disease. It is one that does shorten the lifespan of patients. It is marked by severe agonizing pain crises. And in this example, in this procedure, it wasn’t an attempt to change the genetic code of the mutated globin gene that causes sickle cell disease but rather to compensate for that gene by increasing or switching back on a gene that is normally expressed when we’re fetuses in the womb but then is shut down shortly in the days or weeks after birth.

Dr. Kevin Davies:

But that gene is still sitting there in our genome. It’s still perfectly intact, perfectly functional if only there was a way to just turn the rear stat back on, this is what these teams have done, and the results are fantastic because this fetal globin gene that is now expressed is able to replace the defective gene, the beta-globin gene, one of the forms of adult globin that is causing the sickle cell disease.

Dr. Kevin Davies:

Since her procedure and operation two and a half years ago now, Victoria has been living a healthy and happy life back home in Mississippi. She’s a mother of four. No more pain episodes that I am aware of, no more lengthy hospitalizations or blood transfusions. Physicians are very loath to use the term cure, but this is as close to a cure as you could possibly have wished for.

Dr. Kevin Davies:

To prove this is not just a flash in the pan, here’s another patient in that trial who was recently interviewed by the BBC Jim Olaghere, “I remember waking without any pain and feeling lost.” He said after his procedure a couple of years ago, “My life was so associated with pain. It was just part of who I am. It’s weird now that I don’t experience it anymore.”

Dr. Kevin Davies:

So a remarkable series of many other companies are pursuing similar or complementary strategies to tackle sickle cell of disease, which is, I don’t need to explain to this audience, has been sorely neglected in terms of funding and public education, even though it was literally known as the first molecular disease when the genetic basis was uncovered about 70 years ago.

Dr. Kevin Davies:

But that’s not the only place where CRISPR has shown early clinical success. The other big story which made headlines around the world came from another biotech company, Intellia Therapeutics, published in the New England Journal as well in the summer of 2021. This is for a much less well-known disorder, a liver disorder, a genetic disorder called Transthyretin Amyloidosis. And this was notable for two major reasons.

Dr. Kevin Davies:

The use of CRISPR was again not to finesse or to make a specific base change. It doesn’t quite have the precision to do that. But in this case, the researchers didn’t need to do that. They were trying to prevent the production of a toxic protein caused by this genetic mutation. So using CRISPR, they were able to target a particular sequence in the genome in question, and when the cell went to repair that gene that had been cut in the video that I just showed you, it frequently adds a base, and now you would normally think, “Well, that’s not a good outcome.” But in this case, it’s an ideal outcome because it now puts the rest of the genetic code out of frame, and that results in what we call a premature stop code on and that prevents the full-length protein, which in this case is a toxic protein from being produced.

Dr. Kevin Davies:

So that was exactly the result that they wanted. And this was notable because it was unlike the sickle cell treatment where cells from the patient were taken, put into the lab, treated, and then reinfused back into the patient. This procedure was done directly into the bloodstream of the patient directing the CRISPR components to the liver. So that was one notable aspect of the work.

Dr. Kevin Davies:

The other was that it didn’t use a viral vector. Most gene therapies use a form of virus to shuttle, to ferry the gene in question, and now CRISPR into the cells that you are targeting, but here they used a non-viral delivery mechanism, which is an exciting, potentially less toxic or should raise less immune consequences potentially than using viruses. So we’re going to see a lot more of that, I think in the future.

Dr. Kevin Davies:

There have been other reports a little bit more anecdotal Editas is another of the original group of founding biotech companies commercializing CRISPR, and they’ve reported early clinical results. Not yet peer review, to my knowledge, for a rare genetic form of blindness called Leber Congenital Amaurosis, and the results were good, but the analysts looking at this felt that there was some caveat. So it’ll be interesting to see how this work pans out when it is eventually published.

Dr. Kevin Davies:

There’ve been early trial results led by Carl June, a leading figure in the immunotherapy world in the cancer space here using a sort of a modified form of CAR T therapy. And this is just a section from the summary of that paper, where they said that the paper published in science again in 2020 demonstrates the feasibility of CRISPR gene editing for at least some forms of cancer immunotherapy. So that’s also pretty exciting.

Dr. Kevin Davies:

Left to be resolved for another day is the small matter of price and getting these treatments, assuming they are eventually approved by the FDA to the patients that need them the most. And this is a problem not just facing CRISPR but, of course, all forms of gene therapy and, indeed, many other forms of leading-edge personalized or precision medicine.

Dr. Kevin Davies:

This is the Novartis drug Zolgensma, a miraculous gene therapy ideally given once and a life-saving drug, but with a price tag of over $2 million. And obviously, the researchers who spent a decade or more researching this and the trials and the innovation that was required obviously required some sort of premium on the price of the drug to get some sort of return on their investment and to fuel the next generation of R&D required to improve on that drug or develop the next wave of drugs. No denying that, but $2 million for a one-time drug, we’ve got to find a better way to not only reward investors and shareholders but help the patients as well. And I don’t have the answer for that, but that may be something we can discuss later on.

Dr. Kevin Davies:

So all of that I think is fairly uncontroversial. It’s very gratifying. It’s moving forward very briskly, and we’re going to see many more trials kick off in the next couple of years. And hopefully, in the next few years, we’ll start to see the first approvals, which would be amazing. That form of genetic therapy is called sematic genetic therapy. But I now want to turn to the far more ethically controversial area of germline gene editing, which was dominated one of the biggest science news stories of the last few years, in particular, 2018.

Dr. Kevin Davies:

So the segue is this nice quote from Jeff Goldblum in Jurassic Park. He was so preoccupied with whether or not you could. You didn’t stop to think if you should. And I think that certainly applies to this gentleman. He Jiankul, I will call him JK for short, was the person at the center of this controversy. He was a talented, academically talented researcher who came out of China went to Rice University in Texas for his Ph.D., and then to Stanford to do a one-year post-doc with Stephen Quake leading biophysicist on Stanford faculty before being lured back to China in 2013, to take up a junior faculty position at a new University in Shenzhen just across the border in mainland China, from Hong Kong.

Dr. Kevin Davies:

He’d had a very eclectic publication record. He had, in fact, published one paper on CRISPR as part of his Ph.D., but none of his papers bore any relation to each other. It was a very diverse set of studies. And this was purely a theoretical study. He wasn’t doing any hands-on experiments with CRISPR, nor did he do any experiments that I’m aware of in that field while he was at Stanford.

Dr. Kevin Davies:

He went back to China to initially launch a DNA sequencing company. That was his first commercial endeavor. It was very successful in its own right. China, of course, a huge market for any new clinical sequencing technology, but somewhere along the way, he became interested, if not fixated, in what some of his colleagues were doing in the area of editing human embryos. And this first began to raise some alarms in 2015 as literally a New York Times story based on this paper published in a very obscure journal called Protein and Cell, not nature or science or in journal medicine.

Dr. Kevin Davies:

But here was a Chinese group just showing, just demonstrating, or announcing really that they had performed some gene editing experiments in human embryos. Now, these were not viable embryos, and they had no intention or no prospect of replanting them for any idea of trying to give birth to gene-edited babies. But this was a proof of principle that CRISPR could work to a degree in the context of human embryos.

Dr. Kevin Davies:

Other groups, including a couple of groups in the United with privately funded, they would not get federal funding to do this work, also did similar kinds of studies, and one based in Oregon got a landmark nature paper when they announced in their work in human embryos, that they were now successfully correcting a gene mutation, a pathogenic mutation in human embryo leading to some pretty sensationalist headlines in the British tabloids.

Dr. Kevin Davies:

JK was watching this, and for whatever reason, we still don’t quite have all the answers, he decided to go one very fateful step further. If you could do this if you could edit and correct genetic mutation in human embryo, what was to stop him. He asked himself from actually recruiting couples and implanting these gene-edited embryos.

Dr. Kevin Davies:

He didn’t declare his intentions in any public forum. He merely confided in a very small circle of trust as it’s been called, including a handful of American physicians and ethicists and scientists who were all taken aback by JK’s plans, but he’d sworn them to secrecy. And I’m sure many of these individuals had questioned and thought, why did they respect that confidence when they knew the severity of what this investigator was doing? Because, of course, you are now by changing the genes in a human embryo, those edits will now populate the entire baby once it is born. Every cell in that body and principle will carry these genetics. And those edits will, in turn, be passed on to the next generation to that person’s children and grandchildren. And so on. We are making permanent changes in the human gene pool by human hand, really for pretty much the first time.

Dr. Kevin Davies:

So in early 2018, this is an email from JK to Stephen Quake, his former Ph.D. supervisor, who was serving as an advisor to his sequencing company, saying that the… First of all, he announced that the woman in his trial was pregnant. And then, later in late 2008, he announced that the baby was born, and he wanted Steve’s advice on how to announce the result, public relations, and ethics.

Dr. Kevin Davies:

Is a screenshot from one of the recruitment sessions in China. We are not shown here a couple being told about the informed consent process. One of these gentlemen is a senior Chinese scientist, well known in Beijing. One of the co-founders of the Beijing Genomics Institute. And this gentleman is Michael [Deme 00:31:16], who is JK’s Ph.D. mentor, and continued to be a confidant to JK.

Dr. Kevin Davies:

Now all of this would’ve come out in a very different way publicly were not for some brilliant investigative sleuthing by Antonio Regalado, reporter for MIT Technology Review. He was in China in October 2018 with a film crew working on a documentary about CRISPR and related things and met JK in an off the record discussion, which I talk about in the book because I found out about it from the producers of the film and they shared with me some extraordinary footage of the moment that JK left that meeting.

Dr. Kevin Davies:

They turned on the video camera, and the producer said to Antonio and his colleagues, “Okay, what did we just hear?” And you could see the light bulbs flicking in Antonio’s mind as he just had a sense that JK was planning or had already indeed embarked on human experiments beyond the experiments that he had described and presented data on in showing on gene editing in primates in animal models.

Dr. Kevin Davies:

That culminated in November Thanksgiving week, Thanksgiving Sunday of 2018 in this bombshell. And I used that word advisedly this bombshell report. China scientists are creating CRISPR babies. Antonio didn’t have proof that babies had been born. JK would not go on the record with him, but the evidence he’d found the smoking gun and indeed proof came just a few hours later when the associated press, who had entered into an exclusive sort of embargoed relationship with JK, they published their paper and JK posted a series of extraordinary videos on YouTube proclaiming the birth, the healthy birth of Lulu and Nana the first gene-edited babies.

Dr. Kevin Davies:

Well, all this was a prelude to a bioethics conference in Hong Kong, which normally would not attract literally hundreds of worldwide media. It’s an absolute scrum here, running the full depth of this beautiful, auditorium at Hong Kong University, I’ve never seen anything like it. I wangled a seat in the front row as He Jiankui strode on stage and tried to defend his actions in editing the DNA of Lulu and Nana. You can see the sequence traces up here.

Dr. Kevin Davies:

He showed no remorse. He showed no regrets. He felt he was doing the right thing, not just for this family but really for China. I would go as far as to suggest what he was trying to do was disrupt a gene that there was good reason to think could make those children immune to HIV. So these were couples. He was recruiting where one partner had HIV.

Dr. Kevin Davies:

But the irony and the sad thing is one of many sad ethical questions is that there was absolutely no need for this editing experiment to even be attempted because there are perfectly valid lab procedures, including sperm washing, that would have successfully achieved the ends he was seeking to achieve.

Dr. Kevin Davies:

I talked about this in my book, and I borrowed heavily from an article by now Pulitzer Prize-winning science writer Ed Yong in the Atlantic. The CRISPR baby scandal gets worse by the day. This is written in the week after the Hong Kong conference where Ed listed fully 15 reasons, not a top 10 list, a top 15 list of why this experiment just shouldn’t have been attempted and caused all sorts of problems, ethical problems.

Dr. Kevin Davies:

The biggest reason for me, I think, comes down to this. There are many others, but this was a quote from a very senior member of the Chinese bioethics community. So this isn’t some Western calling out JK. This is one of his comrades saying, “How could Dr. He and his team change the gene pool of the human species without considering the need to consult other parts of the human species?” And I think that really pretty much sums it up.

Dr. Kevin Davies:

Late in 2019, so a year after that Hong Kong event, we finally got to see extracts from the manuscript that JK was hoping to publish. He was literally aiming to the top journal, the top science journal, nature. And here’s the title page you see at least in this draft, may not have been the final draft, but this is the draft that seems to have been reviewed Michael Dime, his supervisor was a senior co-author on the paper, and here at the end of the summary, JK brags that our claims that we are bringing a novel therapy to control the HIV epidemic. So he had visions of this being used across China, or across the world to control HIV. We anticipate embryo genome editing will bring new hope to millions of families seeking healthy babies free from inherited or indeed non-inherited disorders. So the scale of his ambition, you might say delusion was really pretty extraordinary.

Dr. Kevin Davies:

Well, JK did not receive a kind fate after this all came to light. He went from Hong Kong. He returned home to Shenzhen but was immediately put under house arrest. Or, as it’s known in locally residential surveillance, where he was kept for many months before finally being tried and sentenced to three years in jail, but now I’ve seen several reports that he may be released early very soon. So you may be reading about that in the next few weeks. He was sentenced to three years. He served just over two years. At the moment, he was also imposed a heavy fine, and I think, a lifetime ban from work in this field again.

Dr. Kevin Davies:

Jennifer Doudna is not one to call out her fellow scientists, but she made an exception in writing for Time, the Time 100, a couple of years ago, JK’s fateful decision to ignore the basic medical mantra of do no harm and risk the unintended consequences will likely be remembered as one of the most shocking misapplications of any scientific tool in our history.

Dr. Kevin Davies:

So there’s been a lot of debate, a lot of commissions and reports, of course, since the JK fair fiasco, whatever you want to call it. The most important report to have come out, in my view, is this one, Heritable Human Genome Editing, published in late 2020, co-chaired by Rick Lifton, the President of Rockefeller, and Dame Kay Davies, no relation geneticist at Oxford University to extraordinarily well-esteemed human geneticists and they were tasked with really kind of absorbing what we’ve learned from JK and providing a roadmap to say, are there any circumstances under which this powerful technology could be used?

Dr. Kevin Davies:

To some people’s surprise, they said, “Yes, we could imagine that there are some circumstances they’re very narrow, but there are some situations where this might be an important medical procedure.”

Dr. Kevin Davies:

Now, if you wish to avoid passing on a genetic trait in a family with a genetic disease, more and more families and couples are turning to pre-implantation genetic diagnosis. So that’s a form of IVF where we can fertilize an embryo in-vitro in the lab, in a Petri dish, and then do a little after about four or five days of growth, we can just carefully extract one of the cells or a couple of the cells from this bundle of undifferent cells, and look at the DNA and decide which of the embryos in our dish is carrying the genetic mutation that we do not wish to pass on.

Dr. Kevin Davies:

So this is becoming an increasingly common method. So in those situations where that works, there’s absolutely no reason for gene editing, but if a couple with, say, sickle cell disease or cystic fibrosis wish to have, which are both recessively inherited diseases. So both mom and dad carry two copies of the defective gene. There is no way that technique will work because they don’t have a healthy gene or two healthy genes to select for. So the only way they could have a biological healthy child is if somehow you fixed one or both copies of that deleterious gene. So though that’s pretty much the framework under which this commission said maybe HHGE heritable human genome editing might live to see another day, but they weren’t encouraging it. And there are many safety issues and technical issues that have to be sorted out before then.

Dr. Kevin Davies:

That’s sort of the conventional wisdom, but that doesn’t stop other people. And the rest of the world may not see things that way. In 2019, this geneticist, a Russian geneticist fairly renowned geneticist from everything I can see, Denis Rebrikov in Moscow, announced very publicly that he wanted to follow in J K’s footsteps, not for treating HIV this time, but for treating couples who carry a hereditary form of deafness, but who wanted to have a hearing enabled child.

Dr. Kevin Davies:

So in principle, CRISPR could be used to engineer a fix on that mutated gene. He recruited couples. He got that far before the Russian Health Ministry told him to put his plans on ice, you might say. That following a major sort of declaration from the director of the world health organization that this is premature and very ill-advised, but that doesn’t mean those plans couldn’t be restarted again.

Dr. Kevin Davies:

I don’t see any reason why that may not be lurking in some people’s minds. And here’s another little piece of evidence again, a week after JK presented an email that he received. This was shared publicly by William Herbert from Stanford in an email he received from a clinic, a medical clinic in Dubai, saying, “We are interested in partaking in a course regarding CRISPR gene editing for our embryology lab. Do you offer such training courses?”

Dr. Kevin Davies:

So CRISPR clinics may yet happen. There was a report on social media just a few couple of months ago about such a clinic existing in Cypress. That clinic seems to have taken down the inflammatory language that suggested they might be offering CRISPR for certain indications. But you can see that this is open for potentially some form of abuse.

Dr. Kevin Davies:

So in the last few minutes, one of the reasons CRISPR won the Nobel Prize is that it’s not just about curing genetic diseases. I want to say two things. One is it opens up a myriad of other applications. I’ll give you just a taste of a few in the next couple of slides. It’s also a very easy technique to use. I think that’s one of the reasons the Nobel Prize was awarded so quickly is that it took gene editing out of the specialized hands of a couple of companies or a couple of very well-equipped, talented, experienced labs. And he put it in the hands of just about any researcher. I mean, case in point, JK had no experience using CRISPR and yet felt he could offer it to susceptible couples in China.

Dr. Kevin Davies:

It has really become a technique that is now a mainstay used in research labs in every corner of the globe. And some of the applications are really very exciting. So I showed a picture of George Church earlier in the talk. He, a couple of companies that he’s involved in one is called eGenesis that has graced the cover of science a few years ago where they announced their first results applying CRISPR in pigs. This is not to make extra crispy bacon, despite what the title of the cover might suggest, but for a much more important purpose, this is to generate lines of pigs that are safe for xenotransplantation for organ transplantation. Physiologically pigs are a great mimic for humans. If we could just render their DNA sufficiently inert to, for example, remove any signs of any latent retroviruses in the genome that could potentially be reactivated, obviously, that wouldn’t be a smart move.

Dr. Kevin Davies:

So that and other things are what eGenesis, led by one of George’s former students, Luhan Yang, are doing. And, we’re starting to hear reports of the first trials, the first transplants using pig organs. One not involving eGenesis and not involving CRISPR was attempted recently. Unfortunately, it was a heart transplant, I think. And unfortunately, the patient recently died, but this is definitely going to be something we’re going to see more of.

Dr. Kevin Davies:

Recently, unfortunately, it was a heart transplant, I think. And unfortunately, the patient recently died, but this is, this is definitely going to be something we’re going to see more of. Wouldn’t it be amazing if CRISPR could somehow be used to eradicate malaria? Well, that’s not quite as crazy as it sounds. Gene drives mechanisms to kind of; it’s like adding a poison pill to a species in the wild where you can potentially skew in dealing inheritance to knock down a particular population. And this is not yet been used in Africa, but it’s close to being tried. And I think the idea is that if we could remove the mosquito that transmits malaria, mosquitoes serve no ecological purpose that anyone could really point to. So they wouldn’t be missed in theory.

Dr. Kevin Davies:

So, for a disease that kills hundreds of thousands of young children and babies every year, it probably requires something a little bit more drastic, but of course, it’s not just about the science. It’s about winning the trust of the people who are going to be the guinea pigs for this technology. That may be the bigger battle.

Dr. Kevin Davies:

On the farm livestock, we’re seeing reports of gene-edited cattle for many reasons, including disease resistance plants. Of course, I devoted a chapter in the book to efforts in the US and Europe, and China led by Caixia Gao and Zach Lippman and other investigators name your favorite crop or fruit. And it’s probably under attack by the bacteria or virus or slug or something. And gene editing really is, in a growing number of cases, the only hope to provide lines of crops that, or varies of crops. And it makes sense to use the rational editing that we now have, the tools that we have, rather than just hoping using old-fashioned techniques that we can somehow conjure up the mutants that we want. Indeed, the first CRISPR edited tomato just went on sale in Japan. A tomato packed with an alleged in nutritional content. So we’ll look for that and potentially hitting the stores closer to home.

Dr. Kevin Davies:

Here’s George, again, with another of his pet projects. This is a woolly mammoth model in life-size in Siberia. And George has received a lot of press for trying to resurrect the woolly mammoth, not because he wants to preside over some crazy theme park, but because the idea of these creatures roaming the frozen Tundra of Siberia could be very important for keeping the permafrost tapped down and preventing ridiculous amounts of methane from leaching into the atmosphere. So that’s the goal. And his company his new company, is called Colossal, which aims to do that by editing the genomes of the woolly mammoth, nearest neighbor, the Asian elephant.

Dr. Kevin Davies:

The CRISPR Journal, the journal I founded a few years ago, we’ve just published a paper this week on work towards a CRISPR Kitty. So this is a high potentially hypoallergenic cat where CRISPR could be used to disrupt the known gene that causes most of allergic reactions.

Dr. Kevin Davies:

Finally, we’ve spoken about CRISPR in this presentation, but I want to leave you with the understanding that there’s a whole new generation of gene editing tools that I think are going to eventually and steadily supersede much of the fame that CRISPR Cas9 has achieved. Some have been developed in the lab of David Liu. Their techniques called base editing and prime editing. And they’re already showing tremendous promise in treating animal models for diseases like sickle cell or heart disease or a genetic form of premature aging called progeria. So we’re going to hear a lot more about base editing and prime editing and other CRISPR-related tools in the years ahead.

Dr. Kevin Davies:

If you’re interested in learning more about CRISPR, I highly recommend you watch the documentary Human Nature, which came out a couple of years ago, a brilliant film available on Netflix and other streaming services. And I’m really thrilled if you haven’t had the chance already that hopefully, in the near future, have the chance to dig into this in a lot more detail by reading the book, Editing Humanity. So thank you so much for your attention. I hope there are some questions queued up, and I can’t wait to tackle them. Thanks so much.

Alessia Ortega:

All right. Thank you so much, Kevin, for that informative presentation, and yes, we do have some questions. Just remember, if you are in the audience right now, you can continue to submit questions using that Q&A button at the bottom of your screen. And now, let’s get into our first question. So our first question is, are there international ethics committees that have all agreed about the use of this technique, and when will this scientific method be seen as ethical in the field of medical research?

Dr. Kevin Davies:

Thanks for the first question, Alessia. There’s not really an agreement. First of all, the question left out whether we’re talking about germline, genome editing, or somatic gene editing. So I presume we’re talking about germline gene editing, and the reports that I’ve talked about near the end suggest that CRISPR can be used in human embryos in a very ethical fashion, but in a very narrow set of circumstances, but nobody on that commission or indeed most reputable scientists, nobody’s advising this proceed for quite a long time because there’s still good evidence that any time we try to do CRISPR in human embryos, the system is not nearly as precise as we would like to think it is. So I think the jury must stay out, and we must do more basic research before we can even begin to contemplate the responsible use of germline editing.

Alessia Ortega:

All right. Thank you. Our next question is, can you please clarify the off-target mechanism?

Dr. Kevin Davies:

I didn’t want to go into too much detail in the talk, and I won’t hear off-targets. If you think about a genome in the size of the human genome with 6 billion bases, ACs, Ts, and Gs, it is only natural if you do the math on the back of an envelope that if CRISPR is being designed to target a specific gene, the sequence is targeting, which is typically only about two dozen letters long, could by random chance crop up in a completely different sequence, a completely different chromosome somewhere else in the genome.

Dr. Kevin Davies:

So the CRISPR machinery doesn’t necessarily know whether it should land on the gene you want to target on chromosome six or of this other sequence on chromosome 12 that looks 100% identical. So we have to be careful that those sorts of situations don’t crop up, and over the last few years, there’s been a lot of progress in making the CRISPR targeting much more precise and engineering the CRISPR molecule so that the chances of these off-target edits is reduced to essentially background level.

Alessia Ortega:

All right, thank you. On the latest holding and patent interference.

Dr. Kevin Davies:

There was a big patent decision a few weeks ago which came down in favor of the Broad versus the University of California. And rather than try to explain that now I’m going to urge you all in the next couple of weeks, the CRISPR Journal will be publishing a definitive commentary from Jacob Sherkow on that decision. And I could not possibly do any better than that article. So come back to the CRISPR Journal. I will make that article freely accessible, and that will explain all the ins and outs of this decision which all I will say here is that just because one team wins the Nobel Prize, that doesn’t necessarily mean that they, in the eyes of the law are judged to be inventors of a particular technology. And Jacob’s piece will go into all of that.

Alessia Ortega:

Right. So we’ll be on the lookout for the article for sure.

Dr. Kevin Davies:

Yes.

Alessia Ortega:

All right. So our next question is, how can germline editing be regulated effectively?

Dr. Kevin Davies:

Well, I think the commission report, the National Academy Report that I’ve cited and talked about really set it up to individual countries. There’s no way we can just make some sort of universal law that will apply around the world and the way that China or Russia or South America or Africa views gene editing may be very different than the way we view this in the United States or in Western Europe.

Dr. Kevin Davies:

I think that the scientific consensus and the medical consensus has been made very clear, and then must be there is no obvious medical need right now for this technique. And it’s still its very preliminary state to be attempted. But as I also suggested, one could see certain countries or the health organizations or medical establishments in some countries potentially deciding now that the dust are settled on the JK affair, maybe they will say, “You know what? For this particular application, the time is right.” Or maybe some cowboy will set up a CRISPR clinic out of the clutches of the FDA somewhere and give it a go. I hope not, but I can’t possibly rule it out.

Alessia Ortega:

Okay. Thank you. So our next question is, how can Unified International Rules limiting CRISPR editing humanity ever be reinforced worldwide?

Dr. Kevin Davies:

Yeah, I don’t think they can, and they probably won’t for the reasons we’ve just discussed. I think this comes down to individual countries making it clear what is permissible, and yeah, I think I’ve answered that question.

Alessia Ortega:

All right. So how do you see CRISPR’s role versus other gene therapy platforms for life-threatening diseases?

Dr. Kevin Davies:

Yeah, very complimentary. Just because this CRISPR, this gene-editing CRISPR tool exists, doesn’t mean that if anyone thinking about gene therapy is just now suddenly going to, “Oh, we must do CRISPR,” because it’s the cool new toy. Gene therapy has been around, and gene therapies have been approved now for several years. They’ve been very successful for the most part, and there are literally hundreds of trials in progress. So if the best solution for a patient is to simply do “traditional” gene therapy, which is typically providing a healthy copy of the gene that’s mutated in that patient, and we don’t need to worry about editing or CRISPR or anything, then let’s go ahead and do that. Whatever works best for the patient.

Alessia Ortega:

All right. So continuing on that topic of gene therapies, is there a move towards providing therapies for monogenic diseases as a whole versus treating diseases by systems?

Dr. Kevin Davies:

It’s a good question, but I think I would slightly spin it and say, well, really you could think of CRISPR as the platform, the therapeutic platform for treating this whole constellation of monogenic diseases of which there are, as I’m sure the question knows six or 7,000 that we know of. So it’s going to take a long time before we have 6,000 clinical trials targeting each of these diseases.

Dr. Kevin Davies:

But we’re seeing more and more coming along. As companies look to make a name for themselves and find a program where they can succeed and win investment and win approval. They’re probably going to look for areas that are less well covered than other areas like sickle cell is currently. And one company that I showed on the slide halfway through the talk that I’ll quickly mention is Verve Therapeutics which is interesting because they are using or researching the use of CRISPR to tackle not a typical, rare monitoring disease but potentially a heart disease or forms of heart disease with a genetic component, which could potentially open up a market far bigger than treating a typical monogenic disease.

Alessia Ortega:

Al right. Thank you. So you mentioned Verve Therapeutics as one of those companies. Of all the companies that are using CRISPR technology, which three stand out as the most promising and why?

Dr. Kevin Davies:

Well, no companies that I mentioned disclaimer, time should be used for any kind of investment advice. What do I know? But I touched on, I showed a photo at the end of David Liu in his lab at the Broad Institute. And David has founded a number of interesting CRISPR companies. And two that I didn’t mention by name are Beam Therapeutics and Prime Medicine. Beam is now public and will soon be launching clinical trials for sickle cell and other diseases. And the reason for my interest and, dare I say, excitement over this form of technology is that base editing and prime editing allow researchers to make those individual base letter changes. So they can now literally, it’s not just genetic scissors. We’re now talking about genetic tweezers almost, a more finely tuned tool where we can go into a fine and identify the genetic letter that has been mutated and snip it out and perform some chemistry on the DNA to make the fix.

Dr. Kevin Davies:

That’s an incredibly exciting proposition. It doesn’t involve cutting and slicing and dicing the DNA the way that we do that I showed you in the video. So I think those are examples of the next generation of CRISPR-based tools. And there will be many more. So you’ll have to invite me back to talk about those in a couple of years’ time.

Alessia Ortega:

Yeah, absolutely. So onto our next question, selectivity and precision would be key to utilizing clinical. So what is the current state of its development right now?

Dr. Kevin Davies:

I think really following on from that previous question based on prime editing are less damaging to the DNA. They enable the engineering of single-base mutations. So now, sickle cell disease, for example, which is caused by a single letter change now using base editing, we can contemplate changing that letter. We can’t change it using base editing to the normal letter that appears in that position of the beta-globin gene, but the letter that we can change it to is perfectly harmless. So the patient wouldn’t notice.

Dr. Kevin Davies:

So that’s why there’s interest in these newer technologies just been published in the last five years, and now companies have been commercially developed around them that will certainly for the next decade compliment CRISPR Cas9, and then who knows maybe they will become sufficiently popular that they will take over or replace to some extent CRISPR Cas9, but I don’t have a crystal ball. So what do I know?

Alessia Ortega:

All right. Thank you. Our next question is what are the uncertainties surrounding this technology, and what are the limitations in its treatments?

Dr. Kevin Davies:

Yeah, I’d rather glossed over these, and I didn’t mean to. I think there are still many safety concerns with CRISPR. There’s still an awful lot of basic research that needs to be done. Most experts would say the biggest challenge is delivery. So how do we deliver the CRISPR machinery to the liver or the brain or the muscle or the bloodstream or whatever the tissue is, the lungs, whatever tissue we’re trying to fix? And that is not trivial, particularly if you’re trying to replace, for example, whole millions or billions of defects of muscle cells, for example. That’s a challenge. You’ve got to put very high doses. That means higher doses of viruses. And that increases the chances of the body putting on some sort of immune response.

Dr. Kevin Davies:

We know from history over the past 20 years that that can be a devastating life-threatening effect for the patients. So we want to do everything we can to minimize the chances of that happening. And that’s why there’s interest in these non-viral delivery systems. And I think the whole field is taking this very carefully. They have to because there are still reports here and there of adverse events cropping up in gene therapy trials because the viruses that are being used seem to be coinciding with or potentially causing genetic aberrations that are undesired.

Dr. Kevin Davies:

We want to ensure not just for the company sponsoring any given trial but for the field as a whole, the CRISPR doesn’t become tainted or is seen as being unsafe, which would really be a setback for the field when everything has looked so promising for over the last few years.

Alessia Ortega:

All right. Thank you. And speaking of things that are promising, what do you think of direct delivery of Cas9 gRNA complex by conjugating to a targeting antibody Spotlight TX?

Dr. Kevin Davies:

I think the question probably knows more about this company than I do. So I’m going to defer. I did put Spotlight on the slide showing the first or dozen interesting companies in the CRISPR space. There are many others. I think this is promising, but I haven’t really studied it. I haven’t seen any big reports about this, so I will just pause and pass on that one if you don’t mind.

Alessia Ortega:

All right. No problem. So what are the advanced tools for CRISPR in Verve study?

Dr. Kevin Davies:

We’ve talked about base editing and prime editing. I probably won’t belabor that, but I think there are still many new CRISPR enzymes being added to the so-called CRISPR toolbox. So there are groups, including Jennifer Doudna and her colleague at Berkeley, Jill Banfield, and others who are experts at mining the microorganisms that grow in very hostile environments like salt lakes, or under the ocean, or thermal vents, or Yellowstone Park, in geysers, and so on.

Dr. Kevin Davies:

Interest fascinating microorganisms that have evolved all kinds of interesting CRISPR toolboxes that we’ve only begun in the last few years to understand. And as we probe these toolboxes, we find that there are many other enzymes that are part of the crystal machinery with different properties. And, of course, we have a whole slew of hungry investigators looking to adapt these and see where they might be better than the original Cas9, which is the one that’s being used in the clinic. Currently, we’re going to see other Cas enzymes used. I’ve no doubt.

Dr. Kevin Davies:

We’re already seeing other Cas9 enzymes being used in other applications of CRISPR, not therapeutic applications but diagnostic applications. So two other big companies we’ve not yet talked about, Mammoth in California and Sherlock Biosciences on the East Coast, founded by Doudna and Feng Zhang, respectively, are really leading the charge in developing, using CRISPR as a way to now diagnose the presence of infectious viruses. So it was a little too early for us for that technology to be used in the COVID-19 pandemic, but maybe by the time the next pandemic hits, the silver lining might be that we’ll have CRISPR to help us develop new rapid diagnostic tests.

Alessia Ortega:

Right. Well, let’s hope. There is no pandemic for a long time.

Dr. Kevin Davies:

Let’s hope so.

Alessia Ortega:

But yes. Our next question is, what is the most critical point about CRISPR to communicate to the general public? And what is the timeline availability to the general population?

Dr. Kevin Davies:

Yeah, I think the clinical trials are still many more years to go. It’s painstaking, expensive work, and I don’t have a timeline to give for when the sickle cell trial or when the Intellia study on the liver disorder will potentially be ready to apply for clinical approval, probably two or three more years ahead, I would think.

Dr. Kevin Davies:

So on the one hand, the field has moved incredibly quickly. The Nobel Prize in 2020, that was eight years, just eight years after those landmark publications. So that’s pretty extraordinary, I won’t say unprecedented, but that’s pretty extraordinary. And the whole world or scientists around the world are working on this, but for this to really make a difference in the lives of you and me and patients and family members still have a few more years out. Yeah.

Alessia Ortega:

Okay. All right. Our next question is what is the most difficult aspect to pass the regulatory steps and what major safety considerations would you have with advancing gene editing using CRISPR?

Dr. Kevin Davies:

I think all of the trials that are going on now, by definition, really are going as carefully as they can and are working with the FDA and the EMA and the regulatory authorities in just the same way as if they were using gene therapy or just a regular drug. So all of the necessary steps, all of the tests, the toxicology studies, the animal model studies, all of these things are being performed as they should be. And nobody in any of those companies that stand to benefit from seeing one of those gene editing drugs approved, no one would have it be any different because they know that a misstep would be devastating, probably not just for them, but largely for the field as well.

Dr. Kevin Davies:

The key issues that the FDA will be looking at, of course, include the off-targets that we’ve talked about here and the delivery and then ensuring that the manufacturing of these reagents is absolutely pristine, but I think all of those questions are in hand at the moment.

Alessia Ortega:

Okay. Thank you. Our next question is what is the patent situation on CRISPR, and what side effects are there for patients if they utilize CRISPR in the clinic?

Dr. Kevin Davies:

Yeah, I think we talked about that. I’m going to refer everyone to this big paper coming out in two weeks from Jacob Sherkow when the April issue of the CRISPR Journal is published. It’ll be freely accessible. Jacob is a law professor at the University of Illinois. He’s written for us before and for other outlets on this ongoing patent saga. And I think eventually there will be some sort of settlement, is my bet. It’s certainly my hope because this has been a very expensive year, a long period of litigation. It’s not clear that anybody really benefits from that except the lawyers. And there are still unanswered questions. So look for that Sherkow article. It’ll answer anybody’s questions in this particular regard.

Alessia Ortega:

All right. We’ll be on the lookout for it. So, where do you see CRISPR delivery using NLP in immunotherapy?

Dr. Kevin Davies:

Yeah, these are the nano lipoproteins that we use in the entire study. And I think all we need to say is this is a very exciting avenue. I think, in principle if we can get away from using viruses and using these more stealthy, more inert particles that are safe for the body and don’t wake up the immune system, then that’s a good direction to go in. So I think a lot more research in that regard and more trials to come definitely using those sorts of delivery vehicles.

Alessia Ortega:

All right. Thank you. Our next question is, what area of research has CRISPR technology been most used?

Dr. Kevin Davies:

Yeah, I tried to give a few hints in the closing section of the talk. So you saw the CRISPR pigs and the CRISPR woolly mammoth and the CRISPR Kitties. So those are some, but also CRISPR is just a widely used basic research tool for identifying genes involved in cancer pathways or tagging genes to follow during development. And so CRISPR really has become one of those sort of bread and butter tools in the labs. And there’s always new applications for CRISPR.

Dr. Kevin Davies:

So it’s not about how we treat disease or how we produce new healthier crops or disease-resistant crops. Go into any molecular biology lab at any university, and you’ll find CRISPR being used. And what’s great is we’re publishing articles on curricula to get CRISPR into the classrooms, not just at the undergraduate level but even in high schools as well, so that we can turn younger generations of scientists onto the powers of this technology.

Alessia Ortega:

All right, great. Thank you. And onto our last question, what is your view on the influence of chromatin structure/DNA-DS breaks and chromosomal fragile sites that have on CRISPR applications?

Dr. Kevin Davies:

This is another exciting area. I’m sorry. I didn’t have time to get to it in the talk. I think the question is getting into what some people call epigenetic editing. So CRISPR is definitely being applied for study and potential to deliver different types of gene therapy, not where we necessarily change the sequence, the primary sequence of the DNA, but we now do something a little bit at a different layer of the gene regulatory system, where we change the confirmation of DNA or the tagging of different genes so that we can regulate up or down the activity of a particular gene, maybe not by changing the sequence, but by modulating its activity. And you do that by changing the chromatin structure, as you said in the question. So there are definitely a handful of new companies with lots of millions of dollars of funding getting launched. Chroma Medicine is one, Tune Therapeutic is another, and there are others as well. So I think that will be a very big area to keep your eye in the years ahead.

Alessia Ortega:

All right. Well, thank you so much. I am going to ask if you have any closing remarks, any last things you would like to mention before we close.

Dr. Kevin Davies:

No, it’s been a pleasure to give this webinar. I hope everyone enjoys the book. Thank you, Sanguine again for generously offering to deliver the paperback. The book came out in 2020, one day before the Nobel Prize. So that was fortuitous timing, and then the pandemic struck. So it could rather crippled my ability and those of other authors, too, to actually go out and give talks about the subjects. So this has been a wonderful opportunity, and I hope everyone enjoys the book. And please reach out to me if you have any further questions.

Alessia Ortega:

Great. And thank you so much. We are honored to have you here today, and thank you to everyone who joined. For upcoming webinars and to request samples of this webinar, you can visit stage.sanguinebio.com. And we want to thank you all for joining us one more time, and we hope that you have a great day. Thank you, everyone.