Production by Plants: The ultimate option for low-cost and human-friendly biopharmaceuticals!*

Hirokazu Kobayashi

CEO, Green Insight Japan, Inc.

Professor Emeritus and Visiting Professor, University of Shizuoka

The leading cause of death in Japan is cancer, which disproportionately affects the elderly population. Rheumatoid arthritis is also a significant health concern, with 825,000 people suffering from the condition. Biopharmaceuticals, or biologics, have a proven track record of effectively treating these diseases through targeted injections. The global market for these treatments is estimated at 20 trillion yen, equivalent to US$130 billion, annually. As dean and vice president at the University of Shizuoka, I worked alongside Dr. Tasuku Honjo (1942-), the chairman of the board of directors at this university and the 2018 Nobel Prize winner in Physiology or Medicine. He created the cancer treatment drug Obdivo. In 2022, global sales of Obdivo reached 1.5 trillion yen, equivalent to US$10 billion. It's worth noting that biopharmaceutical patents generally expire after 15 years, so many of them have already expired. These drugs are often called "biosimilars" when their structure resembles the original medicines. While I have experience researching plant genes and their expression control mechanisms, consumers in Japan do not widely accept the creation of genetically modified (GM) agricultural products. However, Biopharmaceuticals are highly purified, so production methods are not scrutinized and fall outside GM regulations, and producing them from plants could significantly reduce the cost of these drugs, potentially up to 1/40th of the current one.

Biopharmaceuticals are medications that are manufactured using genetic recombination technology in cultured mammalian cells. Among the top-selling biopharmaceuticals, there is the hTNF-α (human tumor necrosis factor-α) antibody “adalimumab" (marketed as Humira), which is an effective treatment for rheumatoid arthritis and Crohn's disease. However, sugar chains added to proteins in non-human production systems can be recognized as foreign antigens in humans. Our company has developed a new "light-switch" method with red LED for producing biopharmaceuticals using our plant chloroplast engineering technology, eliminating the need for cultured mammalian cells. This commercializes our results (related column) of the Arabidopsis photosystem that discriminates and responds to 680 nm and 700 nm light, published in "Proceedings of the National Academy of Sciences of the United States of America (PNAS)," a leading scientific journal. On the other hand, chloroplast engineering is gentle on humans because it does not add sugar chains. In other words, using tobacco, we have been able to produce a sugar-chain-free, low-molecular-weight protein that can serve as a follow-on drug to Humira. Our primary goal is to commercialize this technology, which has the potential to revolutionize the biopharmaceutical industry, with a global market worth over 30 trillion yen, equivalent to US$200 billion.