Production of canine interferon-producing transgenic strawberry plants
Increase of canine periodontal disease becomes a serious problem according to life-span extension of family dogs. In Japan, it was reported that over 80% of three-year-old or more dogs have contracted periodontal disease, thus, the development of the effective medicine for periodontal disease has been desired. Canine interferon-α (cIFN-α) have been expected as a curative for canine periodontal disease. We achieved successful production of transgenic strawberry plants that produce cIFN-α in their fruits. The cIFN-α producing strawberry is expected as an edible medicine, in fact, we confirmed that this transgenic strawberry had protective and therapeutic effects against canine periodontal disease. Now, the research is aggressively advanced to perform clinical trials.
This research and development has been carried out with Kitasato Institute and Hokkai Sankyo Company Ltd.
 Development of a unspread plant virus vector system
Plant virus vector system is convenient for mass production of recombinant protein (i.e., antibodies, cytokines and vaccine components) in short period. We have previously constructed the Cucumber mosaic virus (CMV) vector which has a very broad host range. However, it is difficult to use plant virus vectors in open fields because of a risk of spreading it to other host plants. We have developed a novel expression system “ Viral vector confinement system (VCS)” using a movement-defective CMV vector, which is localized in inoculated plant cells but can infect systemically only with the aid of transgenic plants that complement viral movement, diminishing the risk of viral proliferation. This system may be applicable for production of many other useful recombinant proteins. This research has been carried out with Hokkaido University.
 Development of hydroponic technologies in closed transgenic plant production system
Transgenic plants which produce pharmaceutical materials should be grown under strictly clean conditions, thus, soil could not be used for cultivation of the plants. We have been developing hydroponic culture technologies to cultivate different plant species such as strawberry, rice, tobacco and potato in closed-type plant production system. All plant species tested have grown well under controlled conditions.
Especially, the hydroponic cultured potato could form many tubers in culture medium, furthermore, the unit area yield of the hydroponic cultured potato exceeded four times those grown open field. Of course, incidence of “Common scab” and “potato cyst nematode”, important potato pests, was not observed.
Plants could be cultivated under highly clean condition without harmful insect, fungi or bacterium, and grown according to production schedule, regardless of the season.
 Gene silencing in plant -alteration of N-glycan structure-
Production of pharmaceutical glycoproteins in plants has many advantages in terms of safety and reduced costs. However, plant-produced glycoproteins have N-glycans with plant-specific sugar residues (core β-1,2-xylose and α-1,3-fucose) and a Lewis a (Lea) epitope, i.e., Gal-β(1-3)[Fuc-α(1-4)]GlcNAc. Because these sugar residues and glycan structures seemed to be immunogenic, deletion of them has been needed. Until date, we could have successfully repressed these glycan structures by repressions of β-1,2-xylosyltransferase, α-1,3-fucosyltransferase and GDP-D-mannose 4,6-dehydratase (GMD) using virus-induced gene silencing (VIGS) and RNA interference (RNAi) in Nicotiana benthamiana plants. Repression of these genes is thus very useful for deleting immunogenic fucose and xylose residues and facilitating the production of pharmaceutical glycoproteins in plants.