GMOs and CRISPR/CAS with Michael Neff

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Show Notes & Resources Mentioned:

View Michael Neff’s faculty page and the Organic Farmers get a Lesson in GMOs article.

Contact Information:

Contact Michael Neff by email at mmneff@wsu.edu or by phone at 509-335-7705.


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Episode Transcription:

[ Music ]

Drew Lyon: Hello and welcome to the WSU Wheat Beat podcast! I’m your host Drew Lyon and I want to thank you for joining me as we explore the world of Small Gains Production and Research at Washington State University. We have weekly discussions with researchers from WSU and the USDA-ARS to provide you with insights with related research on wheat and barley production.

[ Music ]

Drew Lyon: This week we will be discussing genome editing and GMO’s. Our guest is Michael Neff, Professor Crop Biotechnology, and Director of Molecular Plant Sciences, Ph.D. program at WSU. Hi Mike.

Michael Neff: Hey Drew. How are you doing?

Drew Lyon: Good. So, I think all of us have heard the term GMO, but I’m not sure really that we all really understand what that means. Can you tell us what a GMO is?

Michael Neff: So, GMO stands for Genetically Modified Organism. And basically, it’s any biological organism that’s had its genome modified by DNA or RNA base techniques. So, what essentially you see in a GMO is a genome that’s had a piece of foreign DNA or DNA from that exact same plant that’s been inserted into that genome, that plant or animal, or bacterial genome. GMO’s generally in agriculture are plants that overexpress or express different version of a gene, which then encodes a different version of a protein than normal or endogenous protein or gene in the plants’ genome. But there are examples where the transgene, the piece of DNA that we’ve inserted into the genome, is used to silence another piece of DNA. Either in that organism, the plant or for example in a bacteria or a virus or some other pathogen that infects that plant.

Drew Lyon: Ok, so, how does this technology compare to CRISPR or CRISPR/Cas9 which is a gene editing technique. And we’re just starting to hear about this in the general press now and I think a lot of people probably have questions. How does this technology compare to GMO’s and the concept that’s out there on GMO’s?

Michael Neff: That’s a great question, alright. So, let’s start by what is CRISPR/Cas or genome editing in general. So, when we’re doing genome editing, we need two components that are going to be introduced into a living organism cell. In this case, we’ll talk about plants. We need a targeting mechanism that specifically targets a certain region of a gene or genome. And so, that’s done with a piece of DNA that has the same sequence as the target sequence. And then that piece of DNA has another piece of DNA or RNA, actually what we’ve seen is we’re using DNA to encode for or an RNA. RNA stands for Ribonucleic Acid. And in the general system when we talk about the dogma of how gene expression works, we have DNA which is our genome that gets transcribed into RNA which then gets translated into protein. However, RNA’s also have functions on their own. In the case of gene editing, RNA’s are one of the tools that we use for targeting a region of the genome. So, we have a piece of our RNA that is the same basic sequence as the DNA we’re targeting and another piece of RNA that acts like a handle, you can imagine that the cup is a target and the handle carries something else. In this case, that handle is carrying an enzyme that cuts the genome that we’re targeting. The cell then goes and repairs that cut. Sometimes when the cell repairs that cut, it makes a mistake. And as a result, we are inducing mutations into a very specific spot in the genome. This is generally used to either change the sequence or to knock out or delete the ability for that particular sequence to be expressed. Now how do we deliver that RNA and that editing protein? So, the editing protein is called the Cas9 protein. Those can be delivered by a GMO based transgene where we transform an organism with the targeting information as well as the sequence for the Cas9 protein. Those get expressed, scan the genome until they find the target sequence and then make random mutations around that target sequence. Scientists then go in and examine what those mutations look like and then select mutations that are the kind that we want for whatever the purpose of that editing is. We can then use regular genetics to cross out or remove the transgene that caused the mutation. And now what we have is a plant or an animal that is not a GMO in the sense that it no longer contains a foreign piece of DNA that’s been introduced in the genome. But it has a mutation in the genome. Those mutations look identical to naturally occurring mutations in the wild. Except that we have targeted where they occur and then we’ve screened and selected for them. Now, I said that we can use transgene or a piece of GMO DNA in order to bring those tools in, but there are groups that have expressed the RNA targeting sequence and the Cas9 protein, packaged them in a set of molecules and then introduced those molecules into a cell where the cell gets mutated without ever even generating a GMO. So, CRISPR/Cas is not, we can generate CRISPR/Cas using a GMO approach, or we can generate CRISPR/Cas in a non-GMO approach, but once-either way, once we’ve removed the work horse, the targeting sequence and the Cas9 enzyme, then we’re basically looking at something that looks just like a naturally occurring mutation in the wild.

Drew Lyon: Very interesting. So, this argument is it a GMO or not a GMO? Is that going to continue going forward, or are we going to see that this CRISPR 9 allows us to get away from that argument or makes it a much more complicated answer as to whether it’s an acceptable or unacceptable to some groups?

Michael Neff: So, the reason I said, “Oh that’s an awesome or excellent question.” Is because we’re now sitting in the gray zone of definitions. And when people were defining GMO’s no one ever envisioned that a CRISPR/Cas like gene editing approach would be available. The groups that are working on non-GMO approaches to do CRISPR/Cas are basically, shall we say betting or assuming, or suggesting that the public may view the actual use of a transgene to make a CRISPR/Cas mutation. That defines that as GMO so, they’re getting around that by not using a transgene. Still the fact that we are editing the genome in a specific place, could be argued by people that we are genetically modifying an organism. But, there are other techniques such as we what we TILLING, or Target Induced Local Lesions in Genome’s. Where basically groups make huge mutagenic populations of a crop, for example, wheat. And we basically just have tons of mutations throughout the genome and then we have a gene that we’re interested in changing. And we screen that huge population for example, where that gene has been changed. That has never been considered GMO, because it’s just naturally occurring mutations. Or induced mutations that look just like naturally occurring mutations. And no transgene. Where we’re in the gray zone is, once the CRISPR/Cas product is done, once that genome has been edited, if we go in and look at that genome and compare it a naturally occurring mutation, or one of these TILLING induced mutations, we can’t tell the difference. They all look the same. The only difference being whatever the mutation is in that region.

Drew Lyon: Very interesting. So, if our listening audience wants to learn a little bit more about these different techniques, is there a place they can go to find some of this information?

Michael Neff: Well there’s a lot of information out there, but I would suggest that they could come and talk with me. I give talks all around the state and the region on both GMO as well as CRISPR/Cas9 based gene editing and some other variants of GMO’s and different approaches that are being used. I am more than happy to talk with anybody about that. There’s a lot of resources on the internet, but of course, you need to look at enough to be able to figure out which is useful information and which is not.

Drew Lyon: Sound advice. Thank you, Michael.

Michael Neff: You’re welcome. My pleasure.

[ Music ]

Drew Lyon: Thanks for listening to the WSU Wheat Beat podcast. If you have questions for us, that you’d like to hear addressed on future episodes, please email me at drew.lyon@wsu.edu. You can find us online at smallgrains.wsu.edu. You can also find us on social media on Facebook and Twitter @WSUSmallGrains. Subscribe to this show through iTunes or your favorite podcasting app. The WSU Wheat Beat podcast is a production of CAHNRS Communications in the College of Agricultural Human and Natural Resource Sciences at Washington State University. I’m Drew Lyon; we’ll see you next week.