Production or display of foreign proteins using baculovirus and their applications
I. Introduction to Baculovirus:
Baculovirus is the most common insect virus in the wild and agricultural fields worldwide. Because this virus only infects insects and does not affect vertebrates, including humans, it is highly safe and widely approved for use in agriculture, particularly in organic vegetable cultivation to control pests. Due to its long-term use and familiarity, it has been extended as a platform to produce foreign proteins and vaccines. Products produced using the baculovirus system, such as cervical cancer, COVID-19, and many other vaccines, have been approved for human use in several countries, including Taiwan.
The method of producing foreign proteins using baculovirus was first published in 1983, and as a result, there are no longer any main patents restricting its use. Over more than 30 years of research and development, laboratories and industries worldwide have found that this system has high protein yield, safety, and good quality. More than 10,000 related scientific reports have been published. After years of comparative research, it has been globally acknowledged that this system is one of the best tools for producing subunit vaccines. It has become the mainstream for animal vaccine production and is increasingly used for human vaccines. Due to the familiarity and approval of governments worldwide, the prospects for baculovirus-related new products being approved, accepted, and widely used internationally are higher than for other systems.
II. Baculovirus Platform and Market Applications:
Production of large quantities of high-quality foreign proteins: Scientists have discovered that this virus has a strong promoter not found in other cells and microorganisms. Therefore, it can produce large quantities of high-quality foreign proteins when foreign genes are inserted. It can be used to produce vaccines for animals and humans, proteins for laboratory use, and industrial enzymes.
Displaying foreign membrane proteins on the surface of baculovirus: Our laboratory has successfully developed a new tool that can display membrane proteins on the surface of baculovirus. Since protein purification is not necessary, this technology has several innovative applications:
a. Baculovirus displaying foreign membrane proteins can serve as a complete and easily producible new vaccine platform. This is because membrane proteins have antigenicity where they bind to the cell membrane, and if purified from the cell membrane, this characteristic is lost. Additionally, membrane proteins are usually multimers, and if purified, they may lose the antigenicity specific to multimers, often leading to a loss of the ability to produce neutralizing antibodies. Moreover, baculovirus can act as a safe adjuvant, saving a significant amount of adjuvant expenses and additional complications. Therefore, it can be a novel vaccine platform for the rapid production of various vaccines.
b. Baculovirus displaying foreign proteins can act as safe pseudotyped viruses with biological properties like the original harmful viruses: Many highly pathogenic viruses, such as influenza, Ebola, MERS, etc., can only be handled in high-security level laboratories. Research, testing, and vaccine production for these viruses are challenging and expensive. If baculovirus is used to create pseudotyped viruses, they retain the antigenicity and host receptor specificity of the original harmful virus but without pathogenicity. This makes them extremely safe and convenient for experimentation, operation, and vaccine applications, saving a significant amount of time and funds.
Efficiently introducing foreign genes into mammalian cells: Although baculovirus does not infect mammalian animals, when foreign genes are added, it becomes an extremely safe carrier. It can efficiently deliver genes into mammalian cells without disrupting the cells, serving as a tool for safe gene therapy in human tissues. This has extensive applications in the laboratory.
III. Advantages of Baculovirus:
As baculovirus uses an insect system to produce proteins, it is closer to humans than bacteria and yeast evolutionarily. Thus, the proteins produced by baculovirus are functionally and antigenically similar to those of mammalian cells. For example, post-translational modifications such as glycosylation, phosphorylation, and amidation of proteins produced by baculovirus are similar to those in mammalian cells, which are crucial for protein function, antigenicity, and applications. Although proteins can also be produced using mammalian cells, baculovirus generally has a higher protein yield, and faster production speed. It does not pose the risk of harboring common microorganisms and diseases shared between humans and animals. Therefore, the baculovirus system has become one of the main systems for global foreign protein production, especially in the mainstream production of animal and human protein vaccines.
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