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We exploited this link to explore the role of the secreted growth factor termed liver fluke granulin (Ov-GRN-1) in pre-malignant lesions by undertaking programmed CRISPR\/Cas9 knockout of the Ov-GRN-1 gene from the liver fluke genome. Deep sequencing of amplicon libraries from genomic DNA of gene-edited parasites revealed Cas9-catalyzed mutations within Ov-GRN-1. Gene editing resulted in rapid depletion of Ov-GRN-1 transcripts and the encoded Ov-GRN-1 protein. Gene-edited parasites colonized the biliary tract of hamsters and developed into adult flukes, but the infection resulted in reduced pathology as evidenced by attenuated biliary hyperplasia and fibrosis. Not only does this report pioneer programmed gene-editing in parasitic flatworms, but also the striking, clinically-relevant pathophysiological phenotype confirms the role for Ov-GRN-1 in virulence morbidity during opisthorchiasis.<\/jats:p>","DOI":"10.7554\/elife.41463","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T19:05:18Z","timestamp":1547492718000},"source":"Crossref","is-referenced-by-count":79,"title":["Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity"],"prefix":"10.7554","volume":"8","author":[{"given":"Patpicha","family":"Arunsan","sequence":"first","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand"},{"name":"Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington DC, United States"},{"name":"Research Center for Neglected Diseases of Poverty, School of 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