The silkworm, Bombyx mori, is not only an economically important insect but also an increasingly promising chassis for insect synthetic biology. This potential arises from features including a well-characterized genetic background, established germline engineering methods, and exceptional protein synthesis and secretion capacity of the silk gland. Over the past two decades, progress in stable transgenesis, site-specific integration, programmable genome editing, and spatiotemporal gene regulation has expanded silkworm research beyond conventional gene manipulation. In this review, we summarize recent progress in silkworm synthetic biology from four aspects: chassis features, engineering toolkit, representative applications, and future perspectives. We first discuss the main attributes that support the silkworm as an insect chassis, including its genetic and genomic resources, feasibility of embryo manipulation and germline engineering, and its potential for silk-gland-based biomanufacturing. We then outline the core toolkit for silkworm engineering, covering transgenesis and targeted integration, programmable genome editing, tissue-specific and inducible expression systems, and auxiliary approaches such as recombinase systems, gene silencing, and promoter and enhancer trapping. We further highlight representative applications in functional genomics, recombinant protein production, engineering of high-performance silk and silk-based biomaterials, genetic improvement, and biosafety-oriented design. Finally, we discuss bottlenecks, including limited cross-strain adaptability, incomplete standardization of regulatory parts, uncertainty in integration and expression behavior, and biosafety concerns, and consider future opportunities enabled by pan-genomics, multi-omics, artificial intelligence-assisted design, and iterative design-build-test-learn frameworks. Overall, the silkworm is emerging as a programmable and application-relevant insect chassis with potential for both basic research and biotechnology.
Wang et al. (Wed,) studied this question.