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An Interview With Jack Crawford, Chief Executive Officer At Demeetra

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Below is our recent interview with Jack Crawford, Chief Executive Officer at Demeetra:

Q: Could you provide our readers with a brief introduction to your company?

A: At Demeetra AgBio, we are applying our clean Cas-CLOVER™ gene editing technology to the agriculture and biotherapeutics industries. We are “Harvesting Unlimited Opportunities” through this novel biotechnology.

Have you heard of the Nobel Prize winning gene editing technology CRISPR? A recent NPR article sheds light on how new advanced gene editing technologies are being used to treat previously untreatable diseases. Cas-CLOVER can do everything CRISPR can do but with greater precision and less risk of creating unintended mutations. In fact, our sister company, Poseida Therapeutics, is using Cas-CLOVER in the clinic to cure a blood cancer called multiple-myeloma in patients in which all other treatments failed.

Our name, Demeetra, is derived from Demeter, the Greek goddess of agriculture. We are specifically focused on implementing Cas-CLOVER as a force for good in advancing crop traits, biopesticides and plant-based (e.g. cannabinoid) biotherapeutics.

I would like to start out by discussing the vast differences between traditional transgenic-based genetically modified organisms (GMO) and crops derived from advanced gene editing. Humans have been using gene editing for millennia; it just tended to take a very long time, sometimes did not work well, and was instead called breeding. Like all organisms, plants communicate through DNA which we organize into a series of commands: A, T, C & G. When humans began breeding crops for traits such as larger fruit, small changes in the DNA occurred over time. For example, an A may have changed to a T or a bunch of DNA was deleted altogether. We can make these same changes with Cas-CLOVER, as the “molecular scissors” are programmed to cut specific pieces of DNA – resulting in deletions, or what we call “knockouts” for specific genes. Simply put, we can engineer a gene to be turned off by using Cas-CLOVER. We can confirm definitively that there are no changes to the DNA in the plant other than our desired edit – a significant feature that distinguishes Cas-CLOVER from CRISPR. Our approach is much faster and prevents other unwanted traits from coming along for the ride, as is often the case with breeding. Traditional transgenic GMOs contain permanent transgenes that express DNA which produces the trait. You can think of this as copy-pasting something from another organism, whereas Cas-CLOVER, like breeding, simply turns off something that was already in the plant naturally.

A real example of deletions caused by Cas-CLOVER gene editing in plants. A group of DNA (A’s, T’s, G’s & C’s) are deleted from a specific gene causing a knockout, turning off the gene.

Why do we need faster and cleaner advanced agricultural traits? The answer to that is quite simple. Unlike thousands of years ago, there are now billions of people on the planet, and we do not all have 20 acres or spend all of our time growing our own food.

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One USDA report estimated a loss of 14.8 billion pounds of fruit and 23.4 billion pounds of vegetables in 2008 alone. Yet, many traits can be engineered to combat these losses, potentially feeding more people and reducing food costs. Below is an example of GMO tomatoes aimed at reducing such crop loss. Cas-CLOVER can achieve this and many similar outcomes, but can do it without introducing any “transgenes” that can lead to unwanted trait changes. Currently, Demeetra also has collaborations for trait development that will help African banana farmers and North American peas move toward a sustainable, plant-based protein future.

Left: a normal tomato. Right: a GMO tomato from Enhancement of fruit shelf life by suppressing N-glycan processing enzymes

Q: Any highlights on your recent announcement?

A: We recently announced that Cas-CLOVER was used to specifically cut or turn off genes in tobacco. Originally, we envisioned using tobacco as a laboratory model for a proof-of-concept experiment to show that Cas-CLOVER would work in plants. However, upon learning that the FDA is considering getting more aggressive in its long-debated desire to reduce nicotine in cigarettes, we started looking into the genetics of nicotine production in tobacco.

Positive results from a proof-of-concept experiment using Cas-CLOVER in tobacco. Shown here are baby tobacco “shoots” with knockout mutations for the phytoene desaturase (PDS) gene which results in a visually pale and white phenotype.

We found that the nicotine biosynthetic pathway is known in tobacco, and that further downstream from nicotine in the pathway are where the known carcinogens are made. This told us that Cas-CLOVER could be used to specifically turn off nicotine and the carcinogens in tobacco, potentially producing products that are less harmful and/or not addictive.

This was of interest to us because, despite known health problems associated with smoking, the CDC estimates that 34 million Americans smoke cigarettes and says 5.7 trillion cigarettes were smoked worldwide in 2016. We are setting out to first use Cas-CLOVER to turn off the DNA in tobacco that produces carcinogens and then develop a strategy to reduce nicotine in a stepwise fashion; this could help prevent the nicotine black market that both the FDA and tobacco industry believe will emerge if they crack down too quickly.

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Q: Can you give us more insights into your cannabinoid program?

A: I cannot get too detailed because we have not made our efforts public yet, but we are developing a biopharmaceutical which is isolated from cannabis. I would like to point out the differences between cannabis/CBD supplements and our approach – which, if successful, will be an FDA-approved cannabis pharmaceutical like GW Pharma’s Epidiolex.

To gain FDA-approval for marketing a drug, it needs to be proven that it:
1. lacks or is limited in toxicity, 2. is delivered to the body in a way that interacts with the disease, which is typically referred to and measured as “bioavailability” and 3. it actually does what is claimed, which researchers measure as “efficacy.”

Since supplements, including CBD oils, are regulated as food, none of these attributes are required. Bioavailability is tricky, and although a lot of supplements have the potential to do what they say they do, many are simply metabolized and excreted without ever having a chance. For a little social anxiety, a touch of back pain, and a bit more relaxed sleep, CBD supplements probably help; but for our pursuits, more research is required. Stay tuned.

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