iSelect Deep Dive: CRISPR Gene Therapy in Humans

CRISPR gene therapy is one of the most exciting areas of scientific research today, and for good reason. The potential applications of this technology are vast and far-reaching, from developing new treatments for genetic diseases to revolutionizing agriculture and animal husbandry. However, with so much innovation happening in this space, it can be difficult to keep up with the latest developments and opportunities.

Fortunately, there are resources available to help you stay informed and ahead of the curve. For example, a recent deep dive into CRISPR gene therapy provided a fascinating look at some of the key players in this field, including innovative startups like CRISPR Therapeutics, Intellia Therapeutics, and Mammoth Diagnostics.

During the deep dive, experts discussed a wide range of topics related to CRISPR gene therapy, from the legal debates over patent ownership to the potential applications of CRISPR-based disease detection. They also touched on the challenges facing this emerging field, such as the need for better delivery mechanisms for CRISPR systems and the ongoing struggles with regulatory approval.

Despite these challenges, the experts were optimistic about the future of CRISPR gene therapy and the potential it holds for improving lives and solving some of the most pressing problems facing our world today. Whether you’re a researcher, investor, or simply someone interested in the latest breakthroughs in science and technology, this deep dive into CRISPR gene therapy is a must-watch.

So why should you tune in to learn more about CRISPR gene therapy? For starters, the potential applications of this technology are vast and wide-ranging, from developing new treatments for genetic diseases to improving crop yields and animal health. With so much innovation happening in this space, staying informed and up-to-date on the latest developments is more important than ever. Whether you’re a researcher looking to break new ground in this field or an investor looking to capitalize on the latest trends, this deep dive into CRISPR gene therapy is an essential resource. So what are you waiting for? Tune in today and discover the future of gene therapy!


This conference will now be recorded.

Good morning, and welcome to Iselect industry overview webinar series. My name is Luke Wausenschuck, an analyst at the I Select Ventures team, and I’m excited to walk you through today’s presentation and findings.

For those new to these webinars, I Select is an early stage venture capital firm in Saint Louis, Missouri focused primarily on early stage companies in healthcare and agriculture. And I select, we are privileged to live at the forefront of innovation see emerging problems, solutions and macro trends at the very beginning before they make their way to popular culture. We use these deep dives is not only for a wave versus better engage with and understand the science and technology, but also engage experts and entrepreneurs who are driving change and innovation in their responsive fields.

Until recently, gene editing was extremely expensive and took several months even year.

With the discovery of CRISPR and Cas9, costs have shrunk by ninety nine percent and tests can be run-in days and weeks.

Put very simply, CRISPRCAS9 technology is effectively a pair of micro scissors that cuts DNA in a precise directed manner.

With CRISPR, we can go into cells and modify DNA in a way that’s comparable to editing a document. Through the system. We have the potential to switch off the disease causing mutated version of genes to weak fragments of DNA to treat conditions like DMD.

And certain new genes to produce therapeutically relevant proteins.

A few comments before we begin we are not soliciting at investment or giving investment advice in any way whatsoever.

This presentation is general industry research based on publicly available information We’ve invited you to this because you are technologicalists, thought leaders, entrepreneurs, industry experts, early adopting customers or sophisticated investors that are part of the I Select network.

We value your thoughts, questions, comments, and insights into this topic and we’d greatly appreciate it if you was actively engaged during the presentation.

Thank you in advance for your attendance and active participation.

We ask that you put yourself on mute for the time being. However, we hope this to be an engaging and interactive presentation.

So if you have any questions or comments, please feel free to unmute yourself and ask a question or provide commentary.

This presentation is also being recorded and will be available for replay.

And with that, I’m pleased to bring you this week’s deep dive. CRISPR, Gene Therapeutics in humans.

Okay. So before we get going, do a little overview of what we’re going to dive deep into today. First, we’ll talk about CRISPR.

Give a brief overview of what it is in that technology. And then we’ll go into how that’s being applied to gene editing.

Third, we’ll move into the future of gene therapeutics.

Specifically the implications of CRISPR technology, where it’s headed, and also identify some of the current limitations.

Fourth, we’ll talk about CRISPR a little bit more specifically in healthcare, some of the types of therapies that are being reviewed at the time and other recent innovations.

Finally, we’ll conclude with startups, innovation and financing of the space, specifically focusing on cutting edge technologies, venture capital activity, startups and also industry experts and the big CRISPR patent dispute that’s going on right now.

So what is CRISPR? Christopher stands for clustered regulatory interspaced short palindromic repeats.

And basically what it is is a protein RNA complex from ancient bacterial immune system, which is designed to defend against viral attacks.

It’s a specialized region that DNA comprised of nucleotide repeat spacers.

These repeated nucleotide sequences are distributed throughout the CRISPR system and these spacers, which are bits of DNA interspersed along these are interspersed along these repeated sequences. In bacteria, these spacers were made of viral DNA, essentially serving as a memory bank for to identify future viral attacks.

If we look at the system itself, it’s broken down into primarily two components.

Dna cleaver, which comes in the form of either Cas9 or CPF1, a protein that’s programmed to cut foreign DNA and also a targeting mechanism.

Is known as guide RNA. And that’s essentially RNA that tells the enzyme when to snip.

In the ancient bacterial immune system that CRISPR was originally designed for, this is comprised of CR RNA and tracer RNA. But in more recent therapeutic human models, that can be simplified into one strand.

So what does CRister look like in action?

Well, first, the CAS9 protein binds to the guide RNA scanning the bacterial genome for a nucleoside sequence that’s matching the identified viral DNA. And that’s taken from the spacers, the original crispr system.

Upon finding the target site, Cas9 cuts both strands of the DNA double helix, making a double strand break essentially snipping the viral DNA out of the bacterial genome.

There are these built in safety mechanisms called pams or a protospacer adjacent motifs that essentially serve as a safety. And they indicate where on the DNA precisely that cas9 is supposed to cut. And if there’s no pans next to the DNA, then cas9 doesn’t cut. And so this acts as a backup safety mechanism.

What does it look like as a gene editing tool? So once Cas9 and the guide RNA system have cut the DNA double helix, the body then goes into repair mode. And this can happen in a couple of different ways.

First, is in non homologous end joining, reconnection, which is essentially gluing the broken double helix back together. And this typically results in the disruption of problematic genes or the elimination of mutation.

There are primarily two different methodologies to going about this in editing through nonhomologous end joining. One is a cut and revise, and the other is a cut and remove approach.

And these approaches leverage the sales natural repair mechanisms to complete the edit.

When the cell repairs DNA cut by non homologous end joining, it leaves small insertions and deletions in the cut site.

Collectively referred to as Indills.

Nonomologous end joining can use to either cut and revise the targeted gene or cut and remove a segment of the DNA.

In the cut and revised process, a single cut is made, whereas in the cut and remove process, two cuts are made, which results in the removal of intervening segment of DNA.

This approach could be used to delete either small or large segment of the DNA depending on the type of repair required.

There’s another more precise method of editing DNA known as homology direct repair.

And in this situation, it leverages a different DNA repair mechanism, where a DNA template is provided one that is similar to the DNA that’s been cut. And then the cell uses that template to construct reparative DNA resulting in the replacement of a defective genetic sequence with the correct So now let’s take a brief second to step back and understand what CRISPR means for the industry of gene editing. It’s got a significant competitive advantage over current gene editing technologies.

It’s extremely precise. It cuts exactly where it needs to cut on the genome. It’s easily programmable.

And works in almost every cell.

It can edit live cells, it can switch genes on and off, and it’s extremely versatile.

It’s also very inexpensive compared to other methodologies of gene editing.

CRISPR shrunk costs by about ninety nine percent and you can buy a kit for about ninety nine.

Dollars It’s also very time efficient.

So instead of years, it takes merely days or weeks to run these different experiments.

And so what does that mean for healthcare?

That means that we’ve got improved drug and development discovery methods.

So we can rapidly screen cells for activity or functional domains and discover exactly what nucleotides in the DNA sequence are attributed to which express traits.

And ultimately, that means that we have revolutionized how we think about disease therapy.

And it allows us to identify genetic diseases and remove them from our genome. Before we go any further, it felt like it could be useful to briefly go over how CRISPR compares to some of its most direct competing technologies.

So that would be you know, talons and these and these zinc molecules that have been around for a while. But ever since the introduction of in twenty fifteen, we can see that it’s really taken off in terms of how in terms of how companies have been using it.

What this graph represents is the number of times that these technologies were mentioned in earning reports, you know, filed by publicly traded companies. And so while there was while there’s a dip in around twenty seventeen looking at the graph, we can see that that was affected across all gene editing industries.

And that CRISPR has remained on top since its original introduction in the gene editing space in about middle of twenty fifteen.

So now let’s look towards the future.

For good reasons, CRISPR early gene editing can only be conducted on animals. And so as as we are discovering and developing this technology, a lot of the most exciting experiments have been conducted not on humans.

So before we dive into the human therapeutic aspects of CRISPR, and to first talk about some of the exciting genetic modifications that scientists have run on different animals to indicate how exciting this technology really is. So in the upper left, You can see a picture of two different salmon.

And the interesting thing here is that these salmon are actually sisters.

They’re both born from the same mother at the exact same time, but One in the background has a mutated growth hormone that causes the fish to grow extremely fast.

And so what that does is it actually has reduced the growth rate of salmon so that they have reached their peak size for market selling from from three years to eighteen months.

And so raising these raising these growth rates requires significantly fewer resources a normal salmon and can contribute to the production of more sustainable foods.

On the right, we can see a graph of three different pictures taken of pigs that were exposed to extreme cold over the course of a couple hours.

Starting on the left is first exposure in the middle, an hour in, and on the right is two hours in.

And so by inserting a mouse gene into these pig cells in order to better regulate their body temperature, they were actually able to create genetically engineered pigs that had twenty five twenty four percent leaner body fat. And so what that means is that we can get exactly the kinds of cuts that we need based off of simply modifying a couple nucleotides in the genetic sequence.

The bottom left, we have super muscular beagles.

And so this is, hercules and tango. And they were genetically modified to have twice the muscle mass of normal beagles.

And that they did this by having this myosatin gene deleted from the from the beagle at the embryonic stage. And that gene actually inhibits growth in animals.

So by disabling it, they were able to keep on growing and they never reached their peak turnoff point. And finally, on the right, we have these long haired goats.

And long haired goats have been used to disable the FGF5 gene, which limits hair growth.

And so in letting that the hair growth run wild, we’re able to significantly increase the production of Tashmir and and other and other outputs that come from Gopher. So what – of those – the salmon I know are going through approval process, I don’t think they’ve been approved.

I think they work. They work very recently. Are they on can you buy a store now? I think in Canada, it’s just hitting the market. Okay.

How’s the – what about the pigs?

The pigs experiment was conducted in twenty seventeen.

So it’s fairly new and was also conducted in China, which While China has been conducting some of the more radical and revolutionary, risk for application approaches, they’re also pretty they’re pretty secretive about their findings and I don’t believe that’s in the market yet.

And what about the long hair growth?

Long haired goats is also in China. I have to do a little bit more research if they’ve formally commercialized that.

But I know that they’re trying to create essentially breeding pins right now where they’re making entire flocks of of these genetic modified sheet.

Alright. I guess I’m in. Okay. The US has come down to gene edited plants are fine for human consumption.

I take it, they’re looking harder regulation through gene edited animals.

Is that the story?

That’s correct. I mean at this point, we’re only seeing a lot of genetic test run on animals themselves because they’re all experimental, nothing commercial.

For the most part for the most part. Yeah. And then gene editing in humans is being treated like therapeutic. So it’s gone through full FDA approval trials and everything else.

And one of the techniques that they’ve been using a lot recently actually a humanized mouse model, which we’ll get into a little bit later in the presentation.

But that is essentially injecting human cells into mice.

Typically diseased human cells that they’re trying to practice their gene editing techniques on. And so that’s been one of the more tested methods that that we’re seeing at this point. So interestingly, the aquabounty salmon is approved in Canada.

It has been in market.

The FDA has approved it in the U.

S. But they’ve not allowed it to be shipped from Canada. It’s a labeling thing right now.

So the GM protein is actually okay by the FDA, but they just want to make sure that the labeling for import purposes is clear.

You mean by labeling like the next label GM? Yes. I think from consumer protection point of view, protein itself is is technically okayed by the FDA. Is Aqua Valley is just that it grows faster? Do they have other other factors like good question. It’s better. I don’t know if we’re protein.

So moving on from the radical approaches to humans, let’s look towards the look towards the future.

And there’s a lot of exciting new theories and and technologies being developed in the space currently.

And it really holds a lot of exciting new grounds for what’s the common healthcare.

So one of the most exciting advances that is currently in the news is this concept of Xano transplantation.

And that’s essentially growing human organism, human organs in animals. And so specifically pigs have been identified as the ideal candidate for such an operation.

And one startup called EGenesis is looking to do just that, actually. And we’ll touch upon that a little bit later. But they’re working to genetically engineer these human they’re currently working to engineer these human attacking immune responses that are that are native in pigs and also some harmful genes that involve viral bacteria, viral DNA. And they’re looking to cut some of that out so that we can successfully grow either a human kidney or a human liver inside these pigs and so that they can be harvested when necessary.

Another exciting technology is called gene drive.

And what that is basically talking about is altering the genomes that one biological parent is more likely to pass on a specific trait to the offspring.

And this specific approach is being applied to the possibility of eliminating malaria from from the malaria carrying mosquitoes in the wild.

And so the concept behind this would be to release edited mosquitoes that can no longer carry the malaria parasite in their in their body.

With this gene drive genetic genetic technology as well.

So that over time over the course of several generations, just on the cost based off the concept of probability, the wild — the wild mosquitoes will no longer be able to carry the malaria parasite as a whole.

Moving on to the future of healthcare at the bottom there, we see a lot of different interesting applications as well. Designer babies, specifically, is one, of is one of the most exciting approaches. And so a lot of what people are looking to do there is identify exactly which nucleotide sequences affect which characteristics that are expressed in the individual, and then providing a service to parents by allowing them to make changes to their children’s expressed traits. And this has a lot of ethical concerns with it for good reasons, but it’s definitely something that is on the horizon.

Another exciting thing being worked on the CRISPR space is bringing back extinct species.

And this process involves Taking the embryo of the closest living relative of an extinct species and then using CRISPR cas9 to insert the extinct species DNA into that genome where edits need to be made. And so there’s one there’s actually one company doing this called Project Revive and Restore. And it’s run by the the Long Now Foundation.

And they’re actually aiming to bring back the the woolly mammoths currently by taking genetic material from the, I believe it’s the Asian elephant, which is the closest living relative and making the necessary edits. Another interesting concept on the horizon for gene therapeutics with CRISPRzys This concept is called biohacking.

And so there’s a startup actually called the odin, which is selling a DIY bacterial whisper kit on the on website for the retail price of one hundred and fifty nine dollars.

And this whole this whole bacterial kit allows you to self inject yourself with different crispr technologies.

It’s it’s not legal, but it’s still on sale. And it’s pretty interesting.

The the CEO, Joshua, Ziner, I believe his name is, actually self injected himself with crispr modified growth muscle growth hormone.

At a thought in a synthetic biology conference in San Francisco. So clearly, a CEO believes in his technology, but While it’s still relatively improved into the point, it’s definitely something to look forward to in the future.

So with all this excitement, coming up, there’s it’s important to address a couple of limitations that there were researchers and innovations currently facing.

So one of these limitations is something known as off target activity. And that’s unintended activity somewhere else in the genome as a result of DNA tinkering.

And basically, what that what that’s talking about is is the the genome’s a very complex place.

And so sometimes when you’re making a small, minor, adjustment to one aspect of DNA, you can end up getting wildly different consequences in another aspect as well.

And so that’s going to be mindful of.

Sowing else is called mosaic generation, and this is when you have a mix of edited and unedited cells.

And this can result from, ineffectively delivering the CRISPR system to target cells or complications within the CRISPR process itself. And this is a major problem if half of your cells are edited for one DNA, and then the other half of your cells are unedited.

Can obviously create a lot of different problems which is, you know, potentially leading to cancer, but it is avoidable if the gene therapeutic approach is conducted during early stages in the embryo or if it’s conducted upon the stem cells or eggs or sperm cells.

We also have immune system complications that have been known to arise from time to time as well. And this is sometimes because immune system attacks the cast enzymes before they can make gene edit gene edits.

This is a problem that’s currently being sorted out as development progresses.

But it can also be solved to some extent if the crispr system is taking from a more obscure bacterial strain that the human immune system doesn’t recognize.

This, sorry, a fourth limitation that we’re dealing with right now is the surgical precision restraints that CRISPR sometimes faces when targeting different genes across the genome. And this all traces back to the incredible complex nature of DNA itself, and also different cells within your body and how DNA is replicated in each one of those. So we actually have to tinker with specifically how CRISPR is applied in different cells or in different aspects of the genome.

And as as we’re figuring that out, sometimes sometimes experiments fail because just because the the body you know, acted in a way that we hadn’t seen before.

And a final problem of these gene of the gene editing human therapeutics development is is just the initial testing that we’re seeing right now. So a lot of monogenetic disorders, which are the the primary applications for for early testing have such a small patient population that randomized trials are extremely hot difficult to to organize.

So while Christopher is an extremely exciting technology and clearly has some very interesting implications down the road, we currently aren’t there and are still sorting through a lot of these difficulties.

So now we’ll dive into a little bit more about therapies specifically for humans.

And this is an extremely wide field. So Crispr can be applied to numerous different diseases, numerous different types of diseases.

And is gonna real, is really poised to revolutionize healthcare as a whole. And so while we could talk about all these different areas for days, we’re just gonna give a high level overview of a couple of these big topics and then dive deep into until two of those.

So first off, fighting cancer.

Cancer researchers in the UK are currently using techniques with CRISPR with the aim of producing specialized treatment for the individual with cancer.

And so by picking apart cancer cells, researchers can decipher which genes are most important for the disease and survival.

And in the news, in twenty sixteen, Chinese scientists actually began testing CRISPR, edited immune cells in lung cancer sufferers in actual humans. And so while those results haven’t been released, human trials have actually had some success to this point.

Another interesting area is HIV, which is, you know, definitely thought to be one of the the biggest markets for CRISPR technology.

And that’s something that we’ll dive deeper into in a latter slide. But it’s definitely one of the more revolutionary approaches because, to this point, no treatment for HIV has been successful.

We also are excited about a series of, you know, genetic disease therapies that CRISPR’s been able to help alleviate or even solve. One of such is DMD, which is an inherited x linked disease that’s caused by mutations in the gene that instructs the production of dissravin, which is a chemical and muscle cells and a protein required for muscle fiber integrity.

And so DMD causes progressive muscle weakness and shortened life span.

People people inflicted with DMD often passed away some point in their early 30s. And the life that they do live is uncomfortable a lot of time in a wheelchair, and it’s a pretty terrible disease. But And then there’s no effective treatment to date.

So it’s definitely an area of need, but in a recent study conducted from the University of Texas, southwestern, medical center, Researchers used CRISPR to make a single cut at a few strategic points along the DNA in cells derived from DMD patients. And they actually resulted in correcting most of the three thousand gene mutations that caused the disease.

And so as these experiments continue to be run and we start to identify exactly which genes need to be snipped and which ones can be left alone.

We expect these therapies to really take off in fantastic ways. Another important application that CRISPR addresses is antibiotics.

And this is important to you for the super bug epidemic that we’re being to see where a lot of bacterial rains are becoming more resistant to antibiotics that are currently on the market.

And so the University of Wisconsin is actually developing an antibiotic that that makes pathogens essentially commit suicide.

And so you take it via pill, and it uses these bacteriophages or viruses that are harmless to humans to essentially rewire the bacteria to destroy itself, which is a really interesting application of of CRISPR that that could potentially be very difficult for bacteria to fight against.

We also see promising signs of crispr implementation for in vitro fertilization or improving the chances of pregnancy to reduce miscarriages. And so there’s been a lot of different studies being conducted looking into this, specifically a Swedish team led by Frederick Leonard, to edit the DNA in healthy human embryos. And then as usual, Chinese scientists are busy working away on this stuff and correcting genetic mutations and in three normal human embryos.

And then finally, there’s also been some studies looking into different antidepressant approaches, which we’ll talk about on a later slide as well.

So digging into the the HIV applications for CRISPR, About a year ago, so May twenty seventeen, a team led by researchers at Temple University and University of Pittsburgh, conducted an experiment that showed HIV DNA can be completely removed from the genomes of living animals.

And similar experiments have been run before, but this particular one was extremely significant because it was performed on three different animal models.

Including a humanized mouse, where the the mouse had transplanted human immune cells into it, they were inflected with with the HIV virus that was supposed to more accurately simulate the effectiveness of crispr in removing HIV from human killer T cells.

And it’s extremely significant because it was successful and was the first to demonstrate that you know, HIV viral fragments could in fact be completely removed from an infected patient and that viral replication can be ultimately completely shut down these individuals.

What type of modification did they do the T cells to get them to act that way?

So a lot of the problems that come from the HIV virus in killer T cells is There are certain indicators in the genome that, you know, alert the immune system to if there’s something wrong with the the T cell, and HIV has done a very good job of disguising itself. And so what they’ve been able to do is they go in and they remove that that disguise mechanism that that HIV, you know, has has inserted into the human genome killer c cell. And by doing so, the body’s actually actually able to recognize which T cells are healthy and which ones aren’t and then fight against that.

I think they’re right. Okay. Interesting.

So again, this technology is still very new, but early indications would suggest there’s there’s a lot of commas here.

And so while the HIV Therapeutics approach is somewhat well known in the media, There are also some recent advancements that are a little bit more low key in terms of CRISPR’s application, but are also relevant because they demonstrate how how broad the scope of CRISPR therapeutics can be. And so anti the anti depressant drug market, for example, It’s extremely big and hasn’t been very well addressed to with the current medication on the market. So to put this in perspective, about thirteen percent of Americans take anti depressant drugs for depression, anxiety, chronic pain, or sleep problems.

And of the fourteen million Americans clinically diagnosed with depression, about a third of them don’t even find relief from the recommended treatment options or treatment options even available.

And on top of that, we’re looking at the most commonly anti prescribed antidepressant drugs, and they have been approved by the FDA for over thirty years. And so Clearly, we’re seeing a lot of lack of innovation in this space.

And based on the makeup of of the market, it’s missing out on addressing a critical need.

And so what crispr researchers at the Washington University school of medicine and also the Sage Therapeutic company in Boston are actually using CRISPR to target these delta type gaba receptors in the brain using CRISPR and the idea being that gaba, which is an inhibitory neurotransmitter, might actually slow down some of the cognitive processes that lead to the overwhelming and negative feelings that are associated with depression.

And so these neurosteroids are selectively interact with delta type receptors, but developing compounds that selectively bind to specific types of gaba receptors is extremely complicated because of the because of how many different receptor types there are.

Amongst other things.

So using CRISPR, the team was actually able to mutate the delta type gamma receptors specifically isolating them and increasing their role in brain functioning.

And ultimately facilitating the ability for for gaba receptors to bind with the necessary molecules.

And so by better understanding how these different delta gaba gaba receptors in the brain function, the team has verified a specific neuro steroid called BRAKulin.

That could be potentially use of the treatment for postpartum depression in women. And so they actually conducted an experiment that had a lot of success. And of the twenty one, twenty one participants who were in the trial, there was statistically significant findings that said that their depression was improved.

So they’ve gotten actually gotten into Phase one human trials? Yeah. Specifically for that. Sage?

Sage and Washu. Yes. They’ve been doing some joint research together.

Matt asked a question.

Oh, of course.

Hi, this is Bobby.

When wonder, do you happen to know why they’ve selected the gabber receptor as the Borton Here goes Prozac, paxilolol off all those, worked through the search conan, norepinephrine axis in the brain, and gab is not well understood in depression. I wonder how they picked gaba as opposed to serotonin, norepinephrine.

So I could do a little bit more research on that, but But I believe it’s because it’s it’s very hard to deliver the CRISPR system directly into the brain, which is necessary if they’re going after serotonin receptors, whereas gaba receptors can be essentially targeted in other elements of the body and then, you know, can can be can reach the brain through through the bloodstream, which which isn’t, which isn’t possible with serotonin receptors. And do you know, do you recall in the in the, honey, what type of of tests they used to show the improvement?

Did they use the HamD, the Hampton Depression score, or was it some other technique?

So the article that I read didn’t go into specifically which technique was used, but it did mention that it was statistically significant in terms of the numbers of people, the number of people in the trial who who recorded the therapeutic advantages of this bridge?

You know, this is quite interesting.

When Lilly developed Prozac, they had to run clinical trials with hundreds of patients in each trial to get two studies that were positive, so that they could submit it to TA to get the drug approved. So, they had six trials it didn’t work too that showed a statistical significant improvement on HamD.

And that’s what it took to get get Prozac approved the first time.

So, twenty one patients, it’s just this is real. It’s a big deal. Yeah.

And it also – it addresses a pretty significant need as talked about a little bit earlier. And that’s one of the things that I think, not only from a business standpoint, but also from a wellness of the American Society standpoint as well, I think that it’s that, you know, specific with antidepressants, there’s a lot of promise here.

So moving into start ups, innovation, financing within space, We are there’s been a lot of different success to this date.

Specifically, the top funded CRISPR companies have actually some of which have gone public.

And that would be Edith Medicine, CRISPR Therapeutics, and Intelis Therapeutics. And all these came on the scene originally when when the CRISPR technology was was first introduced around twenty fourteen, twenty thirteen.

And they’ve really emerged as the market leaders at this point. And so while while they’ve all been doing big things, it’s actually interesting to note that just this last month, there were published findings that called the precision of CRISPR cas9 gene editing into into question.

And these three public companies took the bit of the hit on on the stock exchange. And so between March ninth and and August twentieth of this year, Edis medicines fell from forty four dollars a share to twenty seven dollars a share. CRISPRapeutics fell from fifty six dollars a share to forty seven dollars a share.

And Intel dropped from thirty four dollars to twenty five.

Dollars The conference personnel at fifty eight. And CRISPR stocks just as a point of reference in August climbed eighteen point seven percent But sounds like from March to August, they were they were down. But — Yeah. — had a banner month in August for what it’s worth.

And so, and yeah, so as much — That just mainly, I apologize of course.

But I know the European Union came out and said something. I want to say late June, early July. And a lot of these fluctuations due in part to just the regulatory environment alone? Or do we see this like across the board with these companies utilizing this technology?

So I kind of I kind of view this, I guess you’d call it investor volatility as, you know, people kind of coming in and out of of of their state and the technology as a whole.


So, you know, like like Tom just mentioned that the the prices are back up to where, you know, where they had just plummeted. And then so they’re doing a lot of going up and down. And I think that as more research comes out and the technology continues to develop, we’re gonna see a lot more stability.

In that space.

But for right now, there’s, you know, there’s there definitely some concerns based off of, you know, conflicting reports that are being published at a time.


And so I think that those sorts of that volatility really reflects the struggles that we’ve seen Crispr innovations at this point. But even still the first half of twenty eighteen was was very encouraging for for CRISPR oriented startup specifically. And we actually saw two supergiant funding rounds, you know, located down below.

We’ve got paralyzed plans. Which focuses on CRISPR gene editing within plants and then also precision biosciences, which as, you know, been leading the some of the biggest pharmaceutical rounds to date. And is working on developing a gene editing platform that’s derived from natural genome editing enzyme, slightly different than CRISPR, but called humming endonuclease.

And so there’s a lot of different technologies that are being spun out and each one offers slightly different advantages and it’s – we’re seeing a lot of interesting things at this point.

So diving down a little bit, I actually stumbled across this graphic on Edis Medicine’s website.

And I really I really like it for a number of reasons, but mainly because I think it does a good job of outlining the broad potential of CRISPR technology and also what some of the specific areas of importance are.

And so in order to develop successful genetic medicines, we really need to do some of the following.

So we need to first achieve the right repair if we cut the genome and repair process doesn’t work, then we don’t get the desired genetic modifications that we’re looking for. We also need to isolate DNA cutting to exactly the right spot on the genome so that we’re not cutting we’re not cutting out the wrong sequence of nucleosides and creating unintended consequences as a result.

Third, we need to understand the differences in editing different types of mutations.

DNA is a very complex you know, system, and there’s there’s a lot we still don’t know about it.

And finally, we need to know and learn and develop different effective methodologies for delivering CRISPR to the right locations.

And so going off of, you know, one of the call one of the callers comments earlier in the in the discussion, you know, the delivery is actually one of the, you know, I guess unsung heroes of the CRISPR system and also one of the the biggest limitation factors to this date. And in the sense of We can use CRISPR to go into any cell and edit it and make some changes. But if we can’t get the CRISPR system into that particular cell, then there’s nothing we can do to change the functionality of it. And so developing new methods of delivering the, you know, whether that’d be through viral vectors or or, you know, RNA or or, you know, lipid nanoparticles.

All those sorts of different delivery mechanisms I think are very important aspect of the approach and as more technologies continue to develop, we’re gonna see even more applications of CRISPR as a whole.

So moving on to some of the innovative startups in the space. We have CEDAGO which is a developer of a precision tool designed to automate genome engineering research.

The company’s tools intend to bring precision and automation to the genome editing process, engineering process, and enabling rapid and cost effective research while also providing consistent results for every scientist. And so this is actually a really interesting platform.

It’s gone a lot of traction to this date, and this is essentially a big database that these scientists can use to help run their crisper experiments. So it provides complete support of every step of the genome editing process, through design, edit, analyzing workflow, and it really allows all the scientists to access CRISPR and advance the research.

It’s the only supporter of full stack genome editing on the market at this point.

And so the, I guess, the main value add here is that it eliminates the time consuming steps that, you know, it takes to design your research experiments. Into seconds as opposed to hours.

And so you can choose from over one hundred and twenty thousand pre mapped genomes in over nine thousand species to get recommended guides to knock out any protein coding gene and minimize the off target effects based off of prior research from networking done with other scientists.

Another interesting startup on the market right now is this sort of called InGenesis, which we talked a little bit about growing human organs and animals earlier in the presentation.

And this is a startup that’s actually doing that in real life.

And so their goal is to make Exano transportation a routine medical procedure for the delivery and safe.

For the delivery of safe and effective human transplantable cells, tissues and organs for hundreds of thousands of patients worldwide. And this is really important, because there’s one hundred and seventeen thousand people in the United States alone who are needing a life saving organ to transplant right now.

And seventy five thousand of those people are on the waiting list. And there’s clear there’s clear demand and need for organs to be grown in some way shape or form because organ donors is just not currently being the demand.

So according to the website, one animal can save about eight lives based off of the organs that can be grown inside of it.

And so when we increase the number of organs available through this process of x trans ex transplantation, then it increases the medical applications by a wide margin.

And then finally, we can look at a startup that’s already exit in the space.

It’s a startup that is developing novel therapeutic design approaches to address diseases associated with or caused by persistent viral reservoirs.

And the company’s novel therapeutics specialize in developing a novel class of nucleus based antiviral therapeutics to eliminate pathogen pathogenetic viral genomes, enabling healthcare providers to treat their patients suffering from devastating and persistent viral infections.

So this company exited to Verb biotechnology for an undisclosed amount in May tenth of of this year. And so it’s exciting to see that we’re already getting startups exiting in this space, considering how new this this field is. I think that we already have startups essentially completing their life cycle and other startups seeing super giant rounds at the time.

And then, you know, more starts doing incredibly innovative and groundbreaking research, it is really a testament for the opportunity that lives within the space.

And then slightly more specific to I select. One of the one of the startups that I found on my research is a company called Mammoth Diagnostics.

And so this is a CRISPR based platform for disease detection.

And so it features a simple paper based test which a liquid sample, usually just saliva is applied and subsequently a color change becomes visible. And then you use it as a smartphone app to simply take a picture of that, scan it. And then you upload that to the cloud and within thirty minutes you have an analysis delivered to you.

And so this startup is at this startup actually recently just closed their Series A funding.

It went for twenty three million raised and completed it in July thirtieth.

So it now holds a post post valuation of about thirty five million dollars So it’s definitely a little bit higher on the end of the spectrum, but it’s a lot of these technologies in the space that are addressing markets with high demand or doing developing innovative technologies.

Tend to have extremely high seed and series A, series B financing rounds. And so it’s definitely a technology that we want to infest in as early as possible because, you know, we’re already seeing fast exits.

We’re already seeing, you know, companies reach supergiant rounds in a matter of years.

And if you’re not getting in early, your your might be boxed out as a help, as a whole because of the the high capital requirement for some of these deals.

How would how is the diagnostics being driven, or how are they using CRISPR for their diagnostics platform?

So the CRISPR based platform comes in in the lab the lab, I guess analysis of it. And so it’s able to based off of the specific color of the of like the, you know, the spit when it — Yeah.

Uh-huh. — used it on the paper.

And then it turns a specific color.

They actually do like a spectrum analysis of that color.

And which their technology can completely read and decipher into what that actually means. And so This is a straight up, just direct to consumer play.

Yeah. And and but the words, how is Chris being Chris are being used in diagnostics of that? Like, what what gene is being modified to perform that service?

So The idea being that the company’s platform uses this CRISPR technology to pick up the bits of genetic material that’s circulating in the blood. And But they do it from a color analysis from your from the way your spit responds to a chemical stimuli?

Yeah. Interesting.


It’s it’s so I believe that a lot of the CRISPR process they haven’t been to the FDA approval process on that.

So have they?

I I’m not sure with the regulation around the FDA approval process would be on this because it’s not, it’s just providing information.

It’s not Yes. This is done. This is just okay. Essentially, is it just like as a supplement? Yeah. So, like, complement initial?

They do have some pretty notable investors.

Kim Cook, for example, and a couple other folks.

I guess it’s more of like a search engine And the CRISPR technology that they’re using is trying to identify certain proteins in the in the sample.

First and then using that for the diagnostic.


Sorry. No, that’s interesting.

It’s really far out there. So Yeah. But do people need to do that though? To people should be doing.

I mean, I think though that the the idea of having this this mobile, you know, genetic analysis — Right.

— kind of take wherever — Right.

— is I mean, a lot of these analysis have to be conducted in in a laboratory and even though crispr dramatically reduces the time and cost associated with it, really something as simple as spitting on paper and taking a picture of it with your phone is about as quick and easy as it gets.

Oh, of course. But I’m looking at it from the perspective because I’ve read several articles. You know, there’s this thing that people are like, just because you can’t doesn’t mean to, you know, get sequence for example. Mhmm. And if they’re identifying these proteins, are those proteins like, I don’t a part of my language, I’m probably getting this wrong, but are those jeans doorman or are they active?

Just because it’s there doesn’t mean you have cancer.

You know what I’m saying? And so is this going to send those both positive messages to, you know, this family out in, you know, Serbia or or whatever that’s doing this just because it might be the latest that I didn’t I don’t know.

Yeah. You know what I’m saying? Because there have been a lot of studies more recently about that. And just because you have something in your data. It doesn’t mean that it’s active.

And I think that that’s one of the things that you know, as we touched upon earlier with the, you know, the research and discovery element of Christopher, just in terms of understanding the aspects of the human genome more. I think we’ll come a long way in helping, you know, the the industry figure out exactly which you know, traits belong to which, though, like you were saying even though you can have, you know, like, a cancer, you know, a cancer trade in in your genome.

It might not be expressed, but we can figure out exactly why that is with the use of CRISPR.

And so I’m not exactly sure No.

Specifically if mammoth diagnostics can can detect it to that level.

Mhmm. But I think that if, you know, any technology could, it it would be crisper.

And so, you know, like a lot of different startups in the space, it’s constant process of innovation. And specifically with CRISPR technology, it’s something that’s moving pretty fast.

Right. Interesting.

So then just moving on to our final slide. It’s important to address the patent issues that are at work with CRISPR and the CRISPR technology as a whole.

So two of the leading researchers and experts in the in the CRISPR field are Fenn Zang and Jennifer do not.

And there are they’re currently involved in in a fierce, you know, legal debate over who owns the rights of the CRISPR human editing patent.

And so, to give a little context, we have time on the bottom, but to summarize where we’re at currently.

The patent office ruled in February twenty seventeen that broad institute’s twenty fourteen CRISPR patent on using CRISPR cas9 to edit genomes based on discovery by Ben Zank, did not in fact interfere with the patent application by UC base, by UC Berkeley by Jennifer Duda. And so Basically, Jennifer’s patent was primarily in the application of editing DNA within cells in a laboratory and Fang Zang’s approach actually applied that to human cells and and live human, you know, cells as well.

And so what’s at stake really here is that once the dust settles around this this CRISPR patent production dilemma, we could essentially see costs, specifically those, you know, the royalties awarded to the patent owner significantly increased.

And so it’s something that’s worth keeping an eye on at this point because of the potential cost implications down the road. But at the moment, it’s, you know, two very brilliant people who are independently driving industries forward who are, you know, also at odds with each other.

But can I ask can I ask a quick question? So of the of the four, five, six companies you talked to talked about who has switch patents.

So Sorry?

Which companies have license? Which patents?

Of the ones that are actively like the publicly traded and the startups out there, which direction are they going to term? Are they getting licenses from both entities?

Are they doing picking a horse and riding that horse? Like, how are they getting access to the CRISPR technology then? What’s kind of the emerging standard for the licensing pattern?


So I think a lot of the at least the licensing royalties haven’t haven’t really been established this point because there’s just been this ongoing this ongoing struggle between these two individuals pictured on the side.

And so Wait. Wait. Wait. Wait. So so the three public companies that have raised and gone IPO, they don’t have rights to either one of these patents.

They have they have more specific rights applied to, you know, how they’re specifically using you know, crispr technology, but the overarching, you know, basic crispr patent of taking this bacterial, you know, immune system and applying it to, you know, changing genetic code within living cells.

That’s owned by one of these two people, and that’s process is still being, you know, unfolding.

And when it when it eventually or a licensing thing. What what Bobby is asking is in order to be able to use technology at all, they had to have licensed it from they those companies had no major choice — Mhmm. — and licensed it from someone otherwise they’d be in violation of.

The patents that have been granted to these guys. Mhmm. So the question is, who were they licensing it from?

So I I believe it’s Ben Zank because he’s this is the one that ultimately — Okay.

— we don’t know. We don’t know. So if we probably we can find out and follow-up.

Hi. This is Carter. Hey, Bobby. One thing we’re seeing and we’re seeing this over with one of our other portcoes. It’s right in the middle of for debate is that Broad, at least, is getting pretty liberal about cross licensing with one instance where a customer of one of our portcoes sort of had an overlapping need and and I’ve rode pretty quickly, executed a license that and so that the coach is Just license from all the institutions and move forward with your product because the value of the product, far exceeds the license cost.

Right. Right. So I was just curious that.

I mean, they had to have had licensing deals figured this all be settled with cross licenses anyway, but, you know And it looks like that’s what’s happening.

And then the other at least on the ag side, who has traits I probably will become the more dominant the dominant player. So you can imagine a company like Benson Hill, that’s got a really deep inventory on photosynthesis on traits.

And so those people are more like our our senses, those are the ones that are gonna more likely seat. I don’t understand on the human side that that doesn’t exactly translate.

Right. Okay. Alright.

And That about concludes the presentation.

So with that, I’d like to thank everyone for their time and attention and listening to me talk a little bit about CRISPR and also for those of you engaged, I’d like to thank you as well.

Thank you. Great job.

Very good and very interesting. I just have one question here.


The company that’s selling the kit where you can inject yourself with some CRISPR technology, what are you injecting yourself with when you do that? Are you injecting yourself with some modified organism that’s supposed to have some biochemical impact on your body? Are you taking your own cells and making them somehow be genetically modified and then inserting those back in your body.

Like, what are people doing when they do this biohacking?

Like, What just So the concept behind biohacking is yet like injecting yourself with with crispr, you know, enzymes, so we’ll essentially, you know So is someone producing those enzymes for them and delivering them to them?

Or are they producing those enzymes?

They’re producing themselves.

Which is not the most difficult thing to do. I mean, it’s it’s very approved.

It’s very risky at the time.

And it’s it’s something that, you know, is really discouraged, you know, to be doing at this stage.

But it’s it’s definitely something that we’re gonna see you know, pretty regularly, I think, down the line.

And so right now, there’s a there’s a couple, you know, radical people doing on themselves. The moment even even as crispr hasn’t been developed enough to consider it safe, but it’s still happening.

Wow. Well, power to them. Yes. Great. Stop sharing. Alright.

Thank you everyone.


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