CRISPR: cutting edge tech for plant breeders

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Plant biologists are excited by the power and simplicity of genome editing, a process that could revolutionize crop trait development that avoids foreign genes and the issues surrounding genetically modified technology.

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Every story has a beginning, a middle and an end.

The story of genetically modified crops began two decades ago, but the tale of that technology may be entering its final chapter.

Many plant scientists believe genome editing, a new method to alter plant DNA, could make GM technology obsolete.

“There’s a whole new tool kit coming, (which) allows genome editing and more sophisticated ways of modifying the plant genome without, I think, giving you a product at the end with this big, hairy GMO label on it,” said Brian Ellis, a University of British Columbia plant scientist.

Ellis is just one of thousands of plant biologists who like the power and simplicity of genome editing. Many think it could revolutionize crop trait development:

“We are at the dawn of a new paradigm in plant breeding,” said Huw Jones, a British plant biologist at Rothamsted Research in nature.com.

“It’s an enormous opportunity, an unfathomable opportunity,” said Martin Spalding of Iowa State University, in the MIT Technology Review.

Most GM crops were developed with transgenic techniques, or genes from other species, to achieve a trait such as insect resistance in corn or a canola plant with herbicide tolerance.

Genome editing is not transgenic. Instead, biologists use what is usually described as “molecular scissors” to alter a gene in a plant’s DNA without introducing foreign genes.

The technology has been around for a while, but the established techniques were cumbersome and expensive.

In 2012, scientists unveiled a new method, called CRISPR/Cas9, to precisely cut and paste a gene in a plant’s genome.

Thomson Reuters predicted in September that the CRISPR inventors would win the 2015 Nobel Prize in chemistry, even though the discovery is only three years old.

The CRISPR technology is particularly exciting because it’s efficient, versatile and relatively inexpensive. Its low cost may permit university and government scientists to quickly develop useful crop traits such as disease resistance in wheat or improved oil content in sunflowers.

University of Minnesota scientists and Cellectis, a biotech firm, have used genome editing to alter the genes of a Ranger Russet potato so it doesn’t accumulate sweet sugars while in cold storage. When deep-fried, potatoes high in glucose turn a darker brown and can produce acrylamide, a potential carcinogen.

Cibus, an American company, has used genome editing to create a canola variety with tolerance for sulfonylurea, a Group 2 herbicide. Cibus hopes to launch its canola in Canada in 2017.

Faouzi Bekkaoui, executive director of the National Research Council’s Canada Wheat Improvement Flagship Program, said genome editing is a much-improved version of mutagenesis.

According to the Canadian Food Inspection Agency website, mutagenesis is a method to change the genetic sequence in a plant using chemicals or ionizing radiation. Scientists have used mutagenesis for decades to develop nearly 3,000 plant cultivars. Clearfield canola, which has herbicide tolerance, was created with mutagenesis.

Mutagenesis is time consuming because plant breeders treat tens of thousands of seeds with a chemical mutagen to induce random DNA mutations. Researchers then plant the seeds and look for individual plants that express the desired trait, such as disease resistance.

Mutagenesis can also cause undesirable DNA changes. Bekkaoui said the harmful mutations must be “cleaned up” through cross breeding before a cultivar can be commercialized.

“The advantage of genetic editing … instead of doing all the random mutations, doing the screening … you go directly to the gene … and make that change,” Bekkaoui said.

“I would say it’s very, very promising.”

Dave Dzisiak, commercial leader for grains and oils with Dow Agro-Science in Canada, said all the major plant science companies have research programs focused on genome editing.

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The beauty of the technology lies in its simplicity and cleanliness.

Ellis said biologists can simply tweak one base in the DNA sequence without residual effects.

“Once you’re done that tweaking, there’s going to be no trace of any activity in the genome.”

The promise of no regulation

While many researchers are passionate about the potential of genome editing, others are equally excited about avoiding plant biotech regulations.

Public opinion surveys indicate that half of Canadians and a similar percentage of Americans think GM food is unsafe. Such a hostile environment has prompted government regulators to intensify their scrutiny of GM crops.

Ellis said the investment required to get a GM trait to market has become prohibitive. In some cases it can cost $100 to $150 million to develop and register a GM trait.

Even if a GM crop variety does receive regulatory approval in North America, a key export market may still reject it. DowAgro and Monsanto are currently waiting on Chinese import approval for GM corn and soybeans with herbicide tolerance.

The massive cost and regulatory uncertainty has made biotech firms reluctant to commercialize a GM trait unless it can be used on tens of millions of acres, Ellis said.

“From where I sit, it seems unlikely that many new products developed through the original technology platforms for gene insertion will make it through the regulatory process.”

Genome editing proponents argue the process is distinct from GMO technology. It’s more like mutagenesis, which isn’t regulated as a GMO.

“The new crop variety does not carry any foreign DNA and could therefore be logically excluded from existing regulations on genetically modified crops,” said Jones.

Such logic makes sense, but regulators may not agree.

“The irony is that mutagenesis is just fine in Europe…. This (should) be even more acceptable, but you never know,” said Peter Pauls, department chair in plant agriculture at the University of Guelph.

The U.S. Department of Agriculture allowed Cibus to launch its herbicide tolerant canola without the regulatory oversight that comes with GMOs. Biotech industry reps say the decision is a sign that genome editing will evade regulation in North America. European authorities are still evaluating the technology.

Jeff Wolt, who specializes in plant biotechnology at Iowa State University, said industry chatter about regulations and genome editing is troubling.

“We need to stop (saying) this is going to allow us to avoid regulation. (That) is going to do nothing but accelerate activist sentiment against the technology,” he said. “That kind of message is not going to work with the public.”

Wolt said scientists should emphasize the positive aspects, such as greater precision, of genome editing to gain public acceptance.

Aaron Beattie, a University of Saskatchewan plant scientist, said making the case that genome editing is different from GMOs could be difficult.

“I think people that don’t like GMOs aren’t going to like genome editing either,” he said.

“It’s too subtle a point to try and pass across to consumers, who already have an issue messing around the genome in any way.”

Dzisiak agreed that explaining the technology is tricky because people are wary of phrases such as genome editing.

“Our science literacy across the population is generally quite low,” he said. “Any time you’re going to (introduce) something new and different … you (need) a good explanation of why it’s safe and what the benefit is.”

Will genome editing replace traditional plant breeding or GMO technology?

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While many believe genome editing is a revolutionary advancement, others aren’t as convinced.

Curtis Pozniak, a University of Saskatchewan plant scientist, said editing one gene has limited power because most “economically important (crop) traits are controlled by many, many genes.”

Therefore, it can’t match the potency of conventional plant breeding.

Pauls said genome editing is an impressive tool, but it cannot replicate the power of transgenic technology.

“You can modify what exists (in a plant’s DNA) in much more precise ways … but you can’t bring in … absolutely new and novel traits,” he said.

“The old technology … there are no species boundaries. That’s the beauty of it. That’s the magic of it.”

For example, scientists pulled a protein from a bacteria to create B.t. corn, a GM variety with insect resistance.

Dzisiak said genome editing can compel a plant to make more of something or less of something, but there are limitations.

“You can’t get the plant to make something it doesn’t have the genetic capacity to do.”

However, he said genome editing can be used in combination with genetic modification to improve the precision of transgenic technology.

“I’m sure 10 or 15 years from now, they’re going to look at how we were doing GMOs and they’ll look at us as being pretty primitive.”

How CRISPR/Cas9 technology works:

  1. An RNA molecule is introduced into a cell. It serves as a guide to locate a specific segment of DNA that contains a gene the researcher wants to edit.
    When the RNA molecule finds the right gene, it attaches itself to that part of the DNA sequence.
  2. Cas9, a bacterial enzyme attached to the guide RNA, cuts the DNA sequence at the desired site in the genome.
  3. Once the genome is broken, the cell will try to repair the cut, which can disable or knock out a particular gene. Or scientists can insert a new segment of DNA into the cut, essentially pasting a gene into the desired location and changing the genome.
  4. Even slight changes to a genome will usually cause it to stop functioning — this is useful when trying to prevent an unwanted trait.

What is…

Mutagenesis:

an evolutionary process in which the genetic information within an organism is changed in a stable manner, resulting in a mutation. Mutagenesis can happen spontaneously or brought on using laboratory procedures.

Genome:

a complete set of genes within a cell. Genomes contain DNA, the instructions needed to build and maintain the organism.

DNA:

deoxyribonucleic acid is the hereditary material found in almost all living organisms. DNA is a code made up of four chemical bases that pair together: adenine (A) pairs with thymine (T), and guanine (G) pairs with cytosine (C). These base sequences bond with sugar and phosphate molecules to create nucleotides, which arrange themselves into two long spirals resembling a ladder, called a double helix. DNA can replicate itself, which is important because cells divide and each requires its own DNA.

RNA:

ribonucleic acid is formed by DNA. It is a single spiral of nucleotides responsible for protein synthesis and transmission of some genetic information.

CRISPR:

acronym for clustered regularly interspaced short palindromic repeats, CRISPRs are segments of DNA that contain short repetitions of base sequences followed by “spacer” DNA called “PAM” (protospacer adjacent motif) that indicates a cell has been exposed to a virus and has adapted a defence to it. These repeating DNA patterns, along with a family of “Cas” (CRISPR-associated) proteins and specialized RNA molecules play a role in bacterial immune sytems. The entire complex of DNA repeats is called CRISPR/Cas. Researchers discovered one specific Cas protein, called Cas9, could identify, cut and replace any gene sequence.

Scientists are now using CRISPR/Cas9 technology to create gene-editing tools that can cut and even replace undesirable genes.

Source: Staff research

Contact robert.arnason@producer.com

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  • RobertWager

    Good article. I agree the call by critics to regulate this technology to a stand still is just beginning. This week Sweden announced gene-editing would not be considered GM. Interesting times

  • richard

    …….And if it continues the legacy of institutionalized arrogance created by GM and its heelers, it will suffer the same fate. The public may be science illiterate but it is not food illiterate….Increasingly educated citizens are seeking taste, nutrition and absence of agribiz contamination in their diets…… More industrial ingredients and antinutrition are just not gonna cut it…..

  • Niklaus Ammann

    Agree that technology should after a short period be taken out of regulation, but it is so new that prudence should be preferred to euphoria, it will be reasonable, to install a Dynamically Scalable System as Wolt and Podevin are suggesting, see

    Wolt Jeffrey D., Wang Kan, & Yang Bing. (2015). The Regulatory Status of Genome-edited Crops. Plant Biotechnology Journal, pp. n/a-n/a. http://dx.doi.org/10.1111/pbi.12444 AND http://www.ask-force.org/web/Genomics/Wolt-Regulatory-Status-Genome-edited-Crops-2015.pdf

    • Harold

      What is he biggest threat to the GM producers? Becoming irrelevant. What if we truly didn’t need them. (like before) Nature (Organics) don’t need them. Perhaps that’s the push from them for “education” and need for laws. After all, that assures the bottom line doesn’t it, with no threat or liability? How can someone be liable If what they are doing is lawful or legally hidden? How much would you lie- for the gains of millions. Mother nature gives to all. That includes the bugs and weeds. If you want more than your share then you toil more but you get a wage for it. Put in one potato and she gives you how many? She grows the grasses for free. In walks the producers who will change this law of Nature, claiming no ill effects. (for a fee) Claiming to know more than Mother Nature. Truly if Mother Nature could name a pest, or a weed: it would be human.