“Illuminating” the silkworm chassis: Synthetic biology‐driven evolution of genetic‐based sexing circuits
Chenyang Li, Mingjie Cao, Bing LiAbstract
The silkworm ( Bombyx mori ), a classical lepidopteran model, is evolving into a highly tractable synthetic biology chassis. In modern sericulture, genetic sexing circuits provide a rational design framework for efficient all‐male rearing, effectively overcoming the gene dosage disruptions and fitness costs associated with traditional radiation‐induced chromosomal translocations. This review systematically summarizes the construction strategies and industrial applications of these circuits. We outline the optimization of sex determination elements and highlight the advantages of far‐red optical markers in penetrating host physical barriers and reducing cytotoxicity. Furthermore, we trace the evolution of genomic manipulation tools from random transposon insertions to targeted CRISPR/Cas9 integration into genomic safe harbors (GSHs). To address circuit instability during multigenerational rearing, protective molecular strategies—including boundary insulators, conditional expression, and automatic excision networks—are evaluated. We also explore the industrial interface that integrates standardized biological optical reporters with artificial intelligence and high‐throughput optoelectronic sorting hardware. Ultimately, engineering principles derived from the silkworm chassis can provide a molecular framework for the sterile insect technique in global pest management, with future directions pointing toward footprint‐free genome editing and dynamic conditional regulation.