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"Illuminating" the silkworm chassis: Synthetic biology-driven evolution of genetic-based sexing circuits
Chenyang Li1, Mingjie Cao1, Bing Li1,2
1School of Life Sciences, Soochow University, Suzhou, Jiangsu Province, China.
Abstract:
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.
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