Concept:
A bioreactor is a device system that utilizes the biological functions of enzymes or organisms (microorganisms) to perform biochemical reactions in vitro. It is a natural function simulator, such as a fermentation tank, immobilized enzyme, or cell reactor,etc.. It has crucial applications in wine, pharmaceutical production, concentrated jam, fruit juice fermentation, and degradation of organic pollutants.
PART.1 Basic principles
Bioreactors may sound unfamiliar, but the basic principles are pretty simple. The stomach is a complex bioreactor inside the human body that processes food. Food is digested by various enzymes in the stomach and becomes nutrients that we can absorb. Bioreactors in bioengineering are reaction devices designed to produce or detect different chemicals by simulating the functions of organisms in vitro. In other words, a bioreactor is a device system that uses the biological processes of enzymes or organisms (such as microorganisms) to perform biochemical reactions in vitro. It is a natural function simulator, such as a fermentation tank, immobilized enzymes, cell—reactors, etc.
Based on the widespread use of immobilized enzymes, people have discovered that natural cells have multifunctional serial reaction systems. Immobilizing cells using physical or chemical methods is a shortcut to using enzymes or enzyme systems. An immobilized cell reactor is like a “life activity function promoter.” Immobilized cell technology began in the 1970s, and its practical application has exceeded that of immobilized enzymes. For example, the United States, Europe, and Japan all use the immobilized bacterial column bed process to produce high-fructose syrup on a large scale.
PART.2 Fallopian tube
In 1993, Dr. Sang of the Roslin Institute in the UK studied the poultry yolk expression system and expressed exogenous proteins in the yolk of eggs. Since the yolk protein is a protein expressed in liver cells, and the content is not high, in 1994, the Chinese Academy of Sciences Microbiology Research Zeng (Jie) Bangzhe, deputy secretary-general of the institute and the Chinese Transgenic Animal Society (preparatory), proposed a poultry transgenic fallopian tube bioreactor, which was the first international study to use the flanking sequences of egg white protein genes to express exogenous medicinal proteins.
Transgenic Animal Newsletter in November 1994 (Glodegg Plan), March 1995 and 1996, the First International Biotechnology and Drug Academic Seminar and Exhibition in Shanghai in July 1995, the 1st and 3rd International Biotechnology and Drugs Exhibition in Beijing in November 1996 The National Academic Symposium on Genetically Modified Animals (Secretary-General Zeng Bangzhe), the 1997 Biotechnology Bulletin, and the creation of the term “oviduct bioreactor” and the system bioscience and engineering website created in Germany in 1999 The concept, methods and technical research of oviduct bioreactor were expounded.
During establishing the 1st International Genetically Modified Academic Symposium in 1996, Zeng Bangzhe contacted relevant genetically modified poultry laboratories in Canada, the United States, the United Kingdom, and Japan. Still, this was the first time anyone was carrying out this subject. Later, he contacted the American Avigenics Company and the University of Georgia R. Professor Ivarie discussed the collaborative research on fallopian tube bioreactors.
In 1998, the American company Avigenics independently conducted large-scale investment, research, and development of fallopian tube bioreactors because Chinese scientist Zeng Bangzhe had gone to Israel. After 2002, there was an international and domestic upsurge in the research and development of fallopian tube bioreactors. In 2003, Science published a review article on Golden Egg.
There are already more than a dozen promising companies in the world developing products using fallopian tube bioreactors. The British Roslin Institute also established a company in 2003, and Dr. Sang presided over the research project, which shifted from the avian egg yolk expression system to the fallopian tube. Bioreactor. The fallopian tube bioreactor will be called the most promising animal bioreactor after the mammalian breast bioreactor.
PART.3 Gene construction
Accessing large quantities of the scarce plasma proteins found in the human body at a reasonable cost was only a fantasy not long ago. However, recent advances in biology and molecular biology have finally made this fantasy a reality. Among them, important discoveries such as injecting exogenous DNA into the pronuclei of germ cells using microscopic techniques, transferring recombinant DNA into mouse embryonic cells, integrating DNA into host chromosomes and germline transmission, and using transgenic (Tg) animals to produce medicinal proteins become possible. In addition, the development of biological technology, such as the acquisition, manipulation, reimplantation, and recombinant DNA of egg cells, has guaranteed the success of transgenic animal bioreactors. Generally, two technical routes exist for producing pharmaceutical proteins in transgenic animal bioreactors. The first is to express the protein of the target gene in homologous tissues; the second is to construct the target gene into a hybrid gene, transfer it into animal embryos, and collect and purify the medicinal protein through the secretory organs of the transgenic animals. The proteins secreted by transgenic animals are processed to resemble the structure of natural human proteins and have completely similar biological activities.
PART.4 Homologous organizations
The most typical example of expressing proteins in homologous tissues is the expression of human hemoglobin in the red blood cells of animals. In the human hemoglobin gene coding sequence, the promoter has two CACCC boxes, while the corresponding pig promoter has only one, and the other one close to it is the CGCCC box. Sharma et al. [1] fused the pig β-promoter with the human β-coding gene and connected the human β-locus regulatory region (β-LCR) and α and ε genes with the β gene of the fusion gene. The vector is transferred into pig embryonic cells, and the recombinant human hemoglobin content obtained from the secreted milk of transgenic pigs is as high as 32g/L.
PART.5 Protein production
Transgenic animals express recombinant proteins, mainly targeting the mammary gland, salivary glands, and bladder. In these expression organs, recombinant proteins can be produced at much higher than normal levels by constructing appropriate vectors and selecting suitable promoters and regulatory sequences. However, the production system should be isolated from the circulatory system as much as possible to reduce the impact of the expressed product on the host animal.
PART.6 Breast Biology
The required target gene is constructed into a vector, plus appropriate regulatory sequences, and transferred into animal embryo cells so that the milk secreted by the transgenic animals contains the required medicinal protein. There is a process from moving the fusion gene into embryonic cells to collecting the protein, including embryo implantation, delivery, and the growth of transgenic animals. From birth to the first lactation of genetically modified animals, pigs, sheep, and cows take 12, 14, and 16 months, respectively, and only female animals lactate discontinuously, generally lasting 2, 6, and 10 months. Large livestock such as cattle and sheep can correctly post-process medicinal proteins to make them have high biological activity. At the same time, they produce large amounts of milk and are easy to build on a large scale, making them ideal animal types for mammary gland bioreactors.
About BaiLun Biotechnology Co., Ltd
BaiLun Bio is a supplier and technical service provider of whole-set bioreactors (fermenter) and control systems. Our products include bioreactors (fermenter), animal cell bioreactors, bioreactor shakers, biological shakers, bottle rockers, control systems for bioreactors, etc. We can produce bioreactors with different volumes of 0.1L-1000KL and make our contributions for China′s bioreactor business to thrive throughout the world.
BaiLun has a contingent of engineers who have rich experience in fermenting processes, biochemical equipment and chemical technology. In addition, we also invite many nationally famous experts and scholars to act as our technical consultants, so as to ensure that our products have strong and steady technological foundations. The innovation of products and the technology leadership are the core parts of our products. Ensuring customer satisfaction is our permanent pursuit. Taking customer benefit as our own responsibility is the core value of Bailun Company.
Our company offers variety of products which can meet your multifarious demands. We adhere to the management principles of “quality first, customer first and credit-based” since the establishment of the company and always do our best to satisfy potential needs of our customers. Our company is sincerely willing to cooperate with enterprises from all over the world in order to realize a win-win situation since the trend of economic globalization has developed with an irresistible force.
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