Successful genome editing of schistosomiasis intermediate host snail — Potential to prevent 200,000 deaths annually worldwide

Distinguished Professor Reiko Kuroda and Designated Senior Assistant Professor Takayuki Uchida from the Frontier Research Institute at Chubu University, Assistant Professor Kouhei Oonuma from the Institute of Agricultural and Life Sciences at Shimane University, and Research Professor Si-Ming Zhang from the University of New Mexico (USA) jointly announced on October 9 that they have successfully attempted genome editing of the intermediate host snail (Biomphalaria glabrata) of Schistosoma mansoni, which parasitizes humans and rodents, and established CRISPR/Cas9-mediated gene knockout technology. This is expected to advance research for prevention and treatment development and contribute to public health. The results were published in Science Advances on October 8.

Schistosomiasis, caused by blood flukes that parasitize blood vessels, triggers diarrhea and bloody stool, and can sometimes induce cancer in specific organs. Occurring in Africa, the Middle East, South America, and Southeast Asia, it affects more than 200 million people worldwide, with 200,000 deaths annually. Even in Japan, there is a history of the disease leading to devastation in areas such as the Kofu Basin and the Chikugo River basin. The specific medication is only effective against adult worms, making the development of therapeutic drugs an urgent priority.

Schistosomes use species-specific freshwater snails as intermediate hosts, where they undergo metamorphosis, and the larvae that emerge from the snails infect humans through the skin. Therefore, rather than eliminating the snails, expectations are rising for disease control methods that interrupt the schistosome life cycle within the snails. However, the mechanisms of infection and immune response in the snails were still not well understood.

In response, knockout technology was established through this research. This made it possible to analyze in detail the immune mechanisms of the intermediate host snail of S. mansoni at the molecular level. Furthermore, by analyzing infection-resistant strains using this technology, the team succeeded in elucidating the functions of genes involved in infection susceptibility and resistance.

Kuroda commented: "The foundation is the embryo manipulation and genome editing technology developed during the process of identifying the snail chirality determination gene. Among the intermediate host snails of Schistosoma mansoni, there are strains that show infection resistance. This paper provides a means to verify the resistance-causing genes. Currently, we are also advancing research to narrow down candidate genes from genetic locus analysis. However, a large grant from the American National Institutes of Health (NIH) was suddenly terminated by the Trump administration on the grounds of foreign nationality, and we have fallen into a dire situation where research cannot continue."

Journal Information
Publication: Science Advances
Title: CRISPR/Cas9-germline editing of Biomphalaria glabrata: A breakthrough in genetic modification of snails that transmit schistosomiasis
DOI: 10.1126/sciadv.adx5889