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Anti-Inflammatory Human Protein Produced in Plants

Tony Jevnikar and Shengwu Ma

Tony Jevnikar, left, and Shengwu Ma inspect engineered plants. (Lawson Health Research Institute)

27 Feb. 2019. Researchers in Canada genetically engineered tobacco plants to economically produce large quantities of a human protein with anti-inflammatory properties. A team from Western University in London, Ontario and Lawson Health Research Institute affiliated with the university describes its discovery in the March 2019 issue of the journal Plant Cell Reports (paid subscription required).

The team led by biologist Shengwu Ma, an adjunct professor at Western and Lawson Institute, and kidney specialist Tony Jevnikar at the university’s medical school is seeking a more productive process for making interleukin 37, a human protein discovered in recent years with anti-inflammatory properties. The protein is among the family of interleukin proteins made by white blood cells that regulate immune system responses. A review published last year notes the anti-inflammatory properties of interleukin 37, in regulating both innate and adaptive immune responses, but noted as well that the protein is expressed in a number of cancers and autoimmune disorders. The researchers say interleukin 37 also has potential for treating stroke, dementia, arthritis, and type 2 diabetes.

The problem with interleukin 37 is the kidney, where it’s made, produces only small quantities of the protein. The authors say attempts to produce the protein in the lab with genetically engineered organisms, such as E-coli bacteria, also result in small quantities and not with processes that can scale up to large enough volumes to make it economical.

To solve this problem, Ma, Jevnikar, and colleagues devised techniques using genetically engineered tobacco as a biorefinery to produce interleukin 37 in larger quantities. While tobacco is associated with products to smoke or chew, having little to do with health, tobacco plants can also be exploited for generating therapeutic proteins, using the plants’ basic biological processes. A well-document example is ZMapp, a drug derived from tobacco plants that was pressed into service as one of the few treatments for the Ebola virus, when outbreaks occurred in West Africa in 2014. In December 2017, Science & Enterprise reported on labs in Australia and Europe engineering tobacco plants to produce human proteins.

The Western-Lawson team experimented with several ways of genetic engineering tobacco plants. The researchers tested transferring genes coding for precursor and mature forms of interleukin 37, as well as fusing it with soybean agglutinin, a protein in soybeans that binds with human proteins. The results show the fusion with soybean agglutinin generates an engineered tobacco plant variety that produces larger quantities of biologically active interleukin 37. The authors conclude their engineered tobacco plants offer a potential bioreactor platform for low-cost, large-scale production of the protein.

Ma believes the engineered tobacco plants can scale-up quickly to produce the proteins. “The plants offer the potential to produce pharmaceuticals in a way that is much more affordable than current methods,” says Ma in a university statement. “Tobacco is high-yield, and we can temporarily transform the plant so that we can begin making the protein of interest within two weeks.” He adds that the technology can be adapted to other plant species, such as potatoes.

Jevnikar says he plans to study interleukin 37 as a way to prevent inflammation during transplants, which often occurs when blood flow is restored to the recipient’s new organ. “I hope that this work will impact a change in how people view plants,” notes Jevnikar, “and hopefully this approach will be a way to provide treatments to patients that are effective and affordable.”

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