CRISPR Gene-Editing in Tomatoes Helps Lower Blood Pressure

Genome-edited food made with CRISPR–Cas9 technology is being sold on the open market for the first time. Since September, the Sicilian Rouge tomatoes, which are genetically edited to contain high amounts of γ-aminobutyric acid (GABA), have been sold direct to consumers in Japan by Tokyo-based Sanatech Seed. The company claims oral intake of GABA can help support lower blood pressure and promote relaxation.

In Japan, dietary supplements and foods enriched for GABA are popular among the public. GABA is a famous health-promoting compound in Japan. It’s like vitamin C. More than 400 GABA-enriched food and beverage products, such as chocolates, are already on the Japanese market. Sanatech, a startup from the University of Tsukuba, first tested the appetite of consumers in Japan for the genome-edited fruit in May 2021 when it sent free seedling CRISPR-edited tomato plants to about 4,200 home gardeners who had requested them. Encouraged by the positive demand, the company started direct internet sales of fresh tomatoes in September and a month later took orders for seedlings for next growing season. Japan’s regulators approved the tomato in December 2020.

Since its inception a decade ago, CRISPR–Cas9 genome editing has become a tool of choice for plant bioengineers. Researchers have successfully used it to develop non-browning mushrooms, drought-tolerant soybeans and a host of other creative traits in plants. Many have received a green light from US regulators. But before Sanatech’s tomato, no CRISPR-edited food crops were known to have been commercialized. Consumers may find food ingredients made with some of the older DNA editing techniques, such as transcription activator-like effector nucleases (TALENs). Indeed, Calyxt in 2019 commercialized a TALEN-edited soybean oil that is free of trans fats. Genome editing tools have also been used to transform a host of ornamental plants. So it was only a matter of time before a CRISPR-edited crop reached palates.

More interesting, however, is that the developer chose this high GABA trait as a first target. GABA is an amino acid and a neurotransmitter that blocks impulses between nerve cells in the brain. The molecule is found natively in the human body and is also ubiquitously present in plants, animals and microorganisms, as well as in food. It can be synthesized by fermenting food and has been developed as a nutritional supplement in some regions.

Sanatech’s researchers increased the amount of GABA in tomato by manipulating a metabolic pathway called the GABA shunt. There, they disabled a gene that encodes calmodulin-binding domain (CaMBD). Removal of CaMBD enables increased activity of the enzyme glutamic acid decarboxylase, which catalyzes the decarboxylation of glutamate to GABA, thus raising levels of the molecule.

Sanatech has been careful not to claim that its tomatoes therapeutically lower blood pressure and promote relaxation. Instead, the company implies it, by advertising that consuming GABA, generally, can achieve these effects and that its tomatoes contain high levels of GABA. This has raised some eyebrows in the research community, given the paucity of evidence supporting GABA as a health supplement. To support the blood-pressure assertion, Sanatech cites two human studies: a 2003 paper on the effect of consuming fermented milk containing GABA and a 2009 paper of the effects of GABA, vinegar and dried bonito. Both studies were conducted in people with mild hypertension and showed blood-pressure-lowering effects.