From Silkroad to Bioroad–Silkworm Biotechnology–

Silkworms have shared history with humans for 5000 years and have significantly contributed to human welfare. Silkworms' ability to produce silk has attracted significant attention as an innovative protein expression system in 21st-century biotechnology, leading to the development of a protein production facility known as the silkworm biofactory. Unlike Escherichia coli expression systems, silkworms can produce recombinant proteins with the added benefits of post-translational modification, easy scalability, and low production costs, as they do not require bioreactors or specialized facilities and expensive media. Numerous recombinant proteins, including secretory and membrane proteins and virus-like particles (VLPs), have been successfully expressed in silkworms and purified, demonstrating their biological functions. Additionally, purification methods have been developed to manufacture recombinant proteins in silkworms. This review provides a comprehensive overview of the silkworm expression system, tracing its development from the past to the present. It highlights advancements in bioengineering related to the production of enveloped and non-enveloped VLPs. Furthermore, the review discusses the technology for displaying antigens on the surface of VLPs, aiming to improve vaccine efficacy through surface conjugations.