Engineered Disease Resistance Silkworm Using Genome Editing

Silk cocoons obtained from silkworms are the primary source of commercial silk, making silkworm an economically important insect. However, the silk industry has experienced significant losses owing to various viral infections. Bombyx mori bidensovirus (BmBDV) is one of the causative pathogens of flacherie disease in silkworms. Although most silkworm strains die after BmBDV infection, certain strains have shown resistance to the virus, which is conferred by a single recessive gene, nsd-2. The +nsd-2gene (the allele of nsd-2, the susceptibility gene) encodes a protein containing a putative 12-pass transmembrane domain, expressed only in the silkworm’s midgut, where BmBDV can infect. In contrast, the nsd-2 gene (the resistance gene) encodes a truncated membrane protein that contains only the first three-pass transmembrane domain. These results suggest that the complete membrane protein may function as a receptor for BmBDV, with viral resistance caused by a defective membrane protein. To take advantage of this relationship between membrane protein structure and viral infectivity, we are currently attempting to artificially generate BmBDV-resistant silkworms using genome editing methods. Theoretically, the deletion of the +nsd-2 gene by genome editing could convert all silkworm strains from virus susceptible to virus resistant.