With a free pass, CRISPR-edited plants reach market in record time

Author: Emily Waltz

CRISPR–Cas9-edited plants can be cultivated and sold free from regulation, the US Department of Agriculture (USDA) is making increasingly clear. The agency gave a free pass to Camelina sativa, or false flax, with enhanced omega-3 oil. And more recently, in October, said that a drought-tolerant soybean variety developed with CRISPR falls outside of its regulatory purview. This laissez faire attitude from the agency shaves years and tens of millions of dollars off the cost of bringing a biotech plant to market. “It eliminates that huge barrier to entry for agbiotech companies,” says Oliver Peoples, CEO of Woburn, Massachusetts– based Yield10 Bioscience (formerly Metabolix) which developed the camelina.

 

It would have taken Yield10 at least six years and $30–50 million to test and collect the data necessary to bring genetically engineered camelina through the full USDA regulatory process, says Peoples. “We did this in two years and [USDA’s decision] took two months, and I assure you we didn’t spend $30 million on it,” he says. The company will present its technology to the US Food and Drug Administration’s voluntary review process, he says.

 

Yield10’s strategy is to allow CRISPR-Cas9 to make double-stranded breaks in the plant’s DNA without a template to direct insertion of a specific DNA sequence. As a result, the plant’s own repair mechanisms rejoin the DNA, giving rise to single-nucleotide inactivating insertions in all three copies of the target gene. Peoples would not disclose which gene his company manipulated in camelina.

 

Camelina oil is used as a biofuel and as a substitute for fish oil in aquaculture. Yield10 will likely make three or four additional edits to the plant line in order to boost camelina’s oil content 25%, and translate the technology to other oilseed crops such as canola and soybean.
 

The edited camelina and the drought tolerant soybean developed by scientists at USDA’s research arm are two of at least five CRISPR–Cas9-edited organisms to sidestep USDA’s regulatory system in the last two years (Table 1). The first such plant to come before the agency, a CRISPR–Cas9-edited white button mushroom (Agaricus bisporus), modified to resist browning, received a free pass in April 2016 (Nature 532, 293, 2016)

 

 

Plants modified using other gene-editing techniques, such as transcription activatorlike effector nuclease (TALEN) and zincfinger nuclease (ZFN) systems, can also fall outside of USDA’s authority (Nat. Biotechnol. 30, 215–217, 2012). The agency in September said it would not regulate a TALEN-edited alfalfa variety with improved nutritional quality. Calyxt (formerly Cellectis Plant Sciences) in New Brighton, Minnesota, developed the crop.

 

The USDA’s change in attitude toward genetic engineering came with the arrival of new technologies to modify plants. Unlike transgenic plants modified using older technologies (Box 1), plants modified with CRISPR–Cas9 and other new gene editing techniques do not require USDA oversight because the resulting plants don’t contain DNA from “plant pests” such as viruses or bacteria. Such organisms were a necessary component in early plant modification tools, such as Agrobacterium-mediated transformation, and triggered regulatory oversight when the US government in the 1980s and 1990s wrote its framework for regulating biotech crops. Although the USDA recently reviewed the old biotech framework, so far, the agency has not broadened the regulatory net to catch organisms made with the newer techniques (Nat. Biotechnol. 33, 1221–1222, 2015).
 

 

Companies that want to know whether their engineered organisms fall outside the USDA’s purview can submit their enquires through the agency’s “Am I Regulated?” route. In all, the USDA has received at least 57 inquires over the past seven years from organizations large and small—from ag giant Bayer to the startup BioGlow—and in most cases has granted the firms a free pass.

 

One such firm is Calyxt, which holds six TALEN-edited crops with non-regulated status, in its pipeline. That includes a high oleic soybean variety that produces oil with increased shelf life and frying characteristics without the need for partial hydrogenation— a process that pumps into food unsaturated trans fats. The company generated the trait by a nucleotide deletion to disrupt two fatty acid desaturase genes called FAD2 and FAD3. Calyxt plans to commercialize the product in late 2018, according to a spokesperson for the company.

 

Lawn and garden company Scotts MiracleGro, in Marysville Ohio, submitted four such inquires related to turf grasses genetically engineered to grow shorter and thicker and tolerate glyphosate (Nat. Biotechnol. 33, 223, 2015) and received non-regulated status for all four. The company is continuing to test and develop two of those: Kentucky Bluegrass and St. Augustine grass engineered to grow more slowly so that they require less mowing, says Bob Harriman, vice president of biotech at Scotts. The company transformed the plants using a gene gun and DNA sequences from non-plant pests.

While the regulatory route for CRISPR edited plants may be getting streamlined, the road to intellectual property licensing remains rather hazy. One recent deal may help define the playing field. The Broad Institute in Cambridge, Massachusetts, and DuPont Pioneer, a division of DowDuPont, which hold key CRISPR patents, said in October they had come to an agreement that will allow companies to obtain a nonexclusive license, while making the intellectual property free for universities and non-profit organizations.