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Journal Publication
Title of Article Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity 
Date of Acceptance 12 December 2018 
     Title of Journal eLife 
     Standard ISI 
     Institute of Journal eLife Sciences Publications, Ltd. 
     ISBN/ISSN 2050-084X 
     Volume 2012-present 
     Issue 8:e41463 
     Month มกราคม
     Year of Publication 2019 
     Page 1-24 
     Abstract Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2012) for cholangiocarcinoma (CCA) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam and Cambodia. 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 geneediting in parasitic flatworms, but also the striking, clinically-relevant pathophysiological phenotype confirms the role for Ov-GRN-1 in virulence morbidity during opisthorchiasis. 
     Keyword Opisthorchis viverrini, Granulin, CRISPR-Cas9, human cholangiocytes cell 
587070018-1 Miss PATPICHA ARUNSAN [Main Author]
Medicine Doctoral Degree

Reviewing Status มีผู้ประเมินอิสระ 
Status ตีพิมพ์แล้ว 
Level of Publication นานาชาติ 
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