Transgenic Silkworms for Recombinant Protein Production: A Comprehensive Review of Expression Systems and Biotechnological Advances
Indrani Nath
Department of Sericulture, Forest College and Research Institute, Mettupalayam, Tamil Nadu Agricultural University-641301, Tamil Nadu, India.
Pankaj Lushan Dutta *
Department of Sericulture, Forest College and Research Institute, Mettupalayam, Tamil Nadu Agricultural University-641301, Tamil Nadu, India.
Manasee Hazarika Ahmed
Department of Sericulture, College of Sericulture, Assam Agricultural University, Jorhat-785013, Assam, India.
Basavaraj Somalingappa Purad
Department of Sericulture, Forest College and Research Institute, Mettupalayam, Tamil Nadu Agricultural University-641301, Tamil Nadu, India.
Mallikarjun
Department of Sericulture, University of Agriculture Sciences, GKVK, Bengaluru, 560065, Bengaluru, India.
O.Ganesh
Department of Sericulture, University of Agriculture Sciences, GKVK, Bengaluru, 560065, Bengaluru, India.
*Author to whom correspondence should be addressed.
Abstract
Recombinant proteins serve as essential components in medicine, diagnostics, and industrial biotechnology. While microbial and mammalian systems have traditionally dominated recombinant protein production, limitations in scalability, cost, and post-translational modifications have prompted exploration of alternative hosts. The domesticated silkworm (Bombyx mori) offers a unique and highly efficient platform due to its robust protein synthesis capacity, well-characterized silk gland biology, and availability of advanced genetic tools. This review explores the evolution of silkworm-based expression systems, including baculovirus-mediated and transgenic platforms, with a focus on tissue-specific expression within the middle and posterior silk glands. Key molecular engineering strategies such as the use of synthetic promoters, enhancers, and site-specific genome editing tools like TALENs and CRISPR/Cas9 are discussed for improving yield and expression fidelity. Applications in therapeutic protein production, including growth factors, antibodies, and vaccine candidates, are presented alongside considerations of biopharmaceutical quality. Challenges in downstream processing, scalability, and regulatory compliance are addressed, and future directions involving synthetic biology, AI-driven bioprocess optimization, and research into non-mulberry silkworm species are highlighted. Collectively, these advances position transgenic silkworms as a next-generation platform for sustainable, scalable, and high-quality recombinant protein production.
Keywords: Transgenic silkworms, recombinant protein production, silk gland bioreactor, piggyBac, baculovirus, TALEN, CRISPR/Cas9, biopharmaceuticals, gene expression