Study on Plant Bioreactors Abroad

In the research of plant bioreactor, the production of various vaccine antigen proteins is the most concerned and the fastest research progress. Viral and bacterial infectious diseases are one of the most important factors threatening human health and quality of life all over the world. Since ancient times, people have been looking for various ways to deal with these infectious diseases. 1778, the British Jenner first discovered that human vaccination can prevent smallpox virus infection. Since then, vaccine has been proved to be the most economical and effective way to deal with infectious diseases, especially viral infectious diseases.

At present, smallpox has been completely eradicated by vaccination, and the occurrence and spread of viral and bacterial infectious diseases such as polio, rabies, tetanus, diphtheria, whooping cough and Japanese encephalitis have been basically controlled worldwide. The form of vaccine has also developed from bacterial vaccine to subunit vaccine, and even DNA vaccine has appeared. However, the vaccines used by people at present are mainly obtained by microbial fermentation or animal cell tissue culture, which requires complex production equipment and procedures, has high production cost and is not convenient for storage and transportation. Therefore, these vaccines are difficult to popularize in economically backward developing countries and are not easy for ordinary people to accept. In addition, some vaccines still have problems of safety and inconvenience. 1992, Americans C.J.Arntzen and H.S.Mason first put forward a new idea of using transgenic plants to produce vaccines. Since then, many laboratories at home and abroad have successively expressed hepatitis B surface antigen, Escherichia coli heat-sensitive toxin B subunit, cholera toxin B subunit, Norwalk virus coat protein and rabies virus G protein in tobacco, potato, tomato, alfalfa and lettuce, and carried out animal and human immune experiments with the antigens expressed by plants, and obtained a lot of valuable research data, which laid a good foundation for the future production of vaccines using transgenic plants (see Annex 2).

PlanetBiotechnology, Inc., located in California, USA, reported the first clinical application study of recombinant medicinal protein from plants. The company uses sIgA, an antibody expressed in transgenic tobacco, to produce a new drug, CaroRxTM, whose main purpose is to prevent and treat dental caries caused by bacteria. Clinical experiments have proved that CaroRxTM can effectively remove Streptococcus mutans from human oral cavity and prevent dental caries in volunteers. The company is also designing and developing some new sIgA antibodies to effectively prevent oral cavity, respiratory tract, digestive tract, reproduction and urethra and other mucosal systems and skin from being infected by some infectious bacteria and toxic factors.

Monsanto, a famous American company, has cultivated a transgenic corn, which can produce 3.7 kilograms of human antibodies reaching the standard of medicinal protein per hectare. If the yield of corn can reach 8.6 tons per hectare, there is still considerable room for improvement in the yield of recombinant protein. Clinical medical researchers plan to inject 250 mg of this antibody protein drug from corn seeds into each cancer patient. Monsanto is also planting transgenic soybeans, which can produce humanized antibody against herpes simplex virus type 2 (HSV-2). Animal experiments show that this antibody can prevent HSV-2 from spreading in the vagina of mice. The in vitro stability and in vivo biological activity of plant-derived antibodies are the same as those cultured in animal cells. Using it, a low-cost treatment method will be developed to prevent and treat some sexually transmitted diseases. American ProdiGene Company and Epicyteparmedicals Company are planning to jointly develop corn-based antibodies, mainly to produce some human mucosal antibodies for passive immunotherapy, because ProdiGene Company has rich experience in expression and extraction in protein, while Epicyteparmedicals Company has a number of related patents.

LargeScaleBiology and Stanford University jointly developed a tumor-specific vaccine, which can be used to prevent malignant growth of cells. They use plant viruses as transient expression systems. Using the modified tobacco mosaic virus as a transient expression vector, researchers can express the type-specific single chain antibody from 38C 13 mouse B-cell lymphoma. After the recombinant virus infects Schistosoma benjamina, single-chain antibody protein can accumulate in extracellular matrix at a high level. The antibody fragment can react with a subtype-specific anti-antibody, indicating that the 38C 13 single-chain antibody produced by plants has been correctly folded. Mice immunized with the 38C 13 single-chain antibody purified by affinity chromatography can produce more than 10ug/ml of type-specific anti-antibody. These mice can resist the lethal dose of 38C 13 tumor attack test, and their protective effect is similar to that after 38c 13 immunization. This rapid virus expression system for producing tumor-specific protein vaccine provides a reliable method for the treatment of non-Hodgkin's lymphoma. The purpose of treatment is to produce special antibodies in patients, which can specifically recognize specific sites on the surface of malignant B cells, so that the target cells are eventually destroyed, while normal cells are not affected.

Another research achievement that has attracted worldwide attention is that Professor IngoPotrykus of Swiss Federal Institute of Technology and his colleagues have been funded by Rockefeller Foundation and European Agricultural Research Program. In 2000, phytoene synthase and lycopene cyclase genes of narcissus were introduced into rice, and rice rich in β carotene (the precursor of vitamin A) was cultivated. The variety name is T309, and each gram of rice contains carotene 1.6mgb. Because of its golden color, it is called "golden rice". At present, about 25-65.438+billion people in developing countries suffer from vitamin A deficiency, and it is precisely because of this disease that 65.438+0.000-20 million children die every year in these countries. Eating this transgenic rice rich in iron and vitamin A will greatly reduce the incidence of anemia and vitamin A deficiency in children in developing countries. At present, the technology has been authorized to the Philippine International Rice Research Institute and a rice research center in India for free to cultivate rice varieties suitable for local cultivation, and large-scale cultivation may begin around 2005.