Protein Production Business using Transgenic Silkworms
Protein Production Technology that Employs Transgenic Silkworms
Silkworms are living things that were repeatedly modified over the thousands of years of silk cultivation to produce bigger cocoons for greater yields of silk thread. At the result, silkworms gained the ability to generate a large amount of bulk silk protein in short period. We focused our attention on this incredible ability, and have spent a lot of time and effort over the last couple of decades researching and developing a transgenic silkworm technology that enables us to produce large amounts of recombinant protein in cocoons.
Our aim is to spark a “Silk Renaissance” by establishing an innovative protein production technology created through the fusion of classical silk culture technology and state-of-the-art transgenic silkworm technology.
Feature of the Protein Production Technology
1.Producing Bulk Protein at Reasonable Prices
We develop transgenic silkworms in which DNA for producing the targeted protein is inserted in the chromosome. The targeted protein is expressed in the silk gland, which is the tissue that synthesizes silk protein. This production system enables us to create large amounts of the targeted protein at a reasonable price by utilizing this explosive ability to synthesize silk protein. The gene introduced in the silkworms is stable and passed on to the next generation, making it easy to scale up production by breeding more silkworms.
Azure-B stained transverse section of a silk thread
A silk thread consists of fibroin fiber, which forms the main part of the thread, and pultaceous sericin that exists in the surrounding fibroin (see the diagram on the right). We succeeded in creating a technology that expresses the targeted protein in the middle part of the silk gland where sericin is synthesized, and secretes it into the sericin part of the thread. The targeted protein expressed in the pultaceous sericin can be easily extracted by dipping the cocoons into a neutral pH buffer.
At the same time, because the sericin and fibroin do not dissolve in the buffer, allowing the targeted protein with a high level of purity to be collected. This also makes it easier to perform the protein purification process after collection.
3.Potential for Post-Translation Modification and Multimer Formation
Unlike microorganisms such as E. coli and yeast, a silkworm is a highly advanced eukaryote that can synthesize a protein with post-translational modifications such as glycosilation and disulfide bond formation. It also supports the synthesis of a multimeric protein with a large molecular weight, and consists of a number of subunits because the silk gland, which is an expressive part of the targeted protein, is the specific organ for synthesizing high molecular silk protein.
Various Protein Production Business using Transgenic Silkworms
1.Manufacturing of Antibodies used for Research Reagents and Diagnostic Products
We can manufacture stable, high-quality monoclonal antibodies using transgenic silkworms. We utilize the antibodies produced from transgenic silkworms in our ELISA assay kits, and we also supply them as materials to diagnostic products makers. Silkworms are not subject to animal protection, and offer the best alternative to production systems that use the ascites of mice.
2.Human Collagen for Cosmetic Materials
We call the human type I collagen α1 chain produced by transgenic silkworms “Neosilk-Human Collagen I”, and commercialized it for use as a moisturizer in cosmetic products. It has also been used in Neosilk Cosmetic and sold as a material. Because this collagen is human-based, there is minimal risk of allergic reactions, making it very safe for the human body.
3.Development of Proteins for Use in Drugs
We have been working together with animal drug makers on the research and development of transgenic silkworm-based materials for animal drugs. We have been also developing transgenic silkworm-based technology for producing proteins that can be used in human drugs, antibody drugs, vaccines, and fibrinogen. We are preparing to construct a manufacturing plant that is GMP compliant because we aim to manufacture antibody drugs in future.
4.Production of Other Proteins
The production system which employs transgenic silkworms is suitable for producing high molecular weight proteins that consist of multiple subunits. We have been using a transgenic silkworm production system to develop proteins that are difficult to produce with other production systems. We can also produce proteins that are required to continuously produce bulk quantities for our customized services. If you have questions, please feel free to contact us.
- Transgenic silkworms that weave recombinant proteins into silk cocoons. Tomita M. Biotechnol. Lett. 2011; 33: 645-654.PMID: 21184136
- Production of a non-triple helical collagen α chain in transgenic silkworms and its evaluation as a gelatin substitute for cell culture.
Adachi T, et al. . Biotechnol. Bioeng. 2010; 106: 860-870.PMID: 20589667
- Production of a recombinant mouse monoclonal antibody in transgenic silkworm cocoons. Iizuka M. et al. FEBS J. 2009; 276: 5806–5820.PMID: 19740109
- A germline transgenic silkworm that secretes recombinant proteins in the sericin layer of cocoon. Tomita M. et al. Transgenic Res.
- Generation of a transgenic silkworm that secretes recombinant proteins in the sericin layer of cocoon: production of recombinant human serum albumin. Ozawa S. et al. J Biotechnol. 2007;128:531-544.PMID: 17166611
- Transgenic silkworms produce recombinant human type III procollagen in cocoons. Tomita M. et al. Nat. Biotechnol. 2003;21:52-56.PMID: 12483223
Note: Retrieve by PMID number in displayed by abstract: http://www.ncbi.nlm.nih.gov
The research achievements made by the intelligent cluster of creative businesses, the Hiroshima Bio Cluster, and National Institute of Agrobiological Sciences (NIAS) have been applied to the development of transgenic silkworm technology.