Silkworm as a Biofactory Insect: A Critical Narrative Review of Recombinant Production Platforms, Product Quality and Translational Readiness

Abstract

The domesticated silkworm, Bombyx mori, has moved from a sericultural resource to an engineered production host for recombinant proteins, virus-like particles, functional silk, and, more recently, heterologous biosynthetic products. Its appeal is biologically distinctive: larvae and pupae support B. mori nucleopolyhedrovirus-based transient expression, whereas the exceptionally secretory silk gland can be genetically reprogrammed to deposit recombinant products into a cocoon that also functions as a dry storage matrix. This critical narrative review evaluates the silkworm as a biofactory by integrating evidence on transient baculovirus systems, stable transgenic silk-gland platforms, emerging silkworm cell lines, host and vector engineering, post-translational processing, downstream purification, representative product classes, scale-up and translational readiness. The evidence indicates that silkworm systems can produce structurally complex and biologically active proteins, multicomponent virus-like particles and engineered silk-associated products at experimentally useful to pilot-relevant scales. The strongest advantages are not universal low cost or intrinsically human-like processing, but the availability of several biologically different production architectures, high secretory capacity in specialised tissues and the possibility of coupling synthesis with cocoon-based capture and storage. Important constraints remain. Glycan composition is platform- and tissue-dependent, baculovirus infection can intensify proteolysis and host contamination, high recombinant load can perturb silk-gland physiology, and downstream recovery can dominate practical manufacturability. Recent batch-scale antibody production and glycan-remodelled lysosomal enzyme studies materially strengthen the translational case, while new high-proliferation silkworm cells may narrow the divide between whole-insect and conventional insect-cell manufacturing. Nevertheless, evidence for current good manufacturing practice reproducibility, comprehensive comparability, regulatory control and techno-economic superiority remains limited. Future development should therefore be product-led: cargo properties, critical quality attributes, tissue environment, processing capacity and purification route should determine the choice of silkworm chassis. On this basis, B. mori is best understood not as a single substitute for established expression hosts, but as a configurable insect biomanufacturing platform whose value is greatest when its biology is matched deliberately to the product.