Journal article

Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity

Patpicha Arunsan, Wannaporn Ittiprasert, Michael J Smout, Christina J Cochran, Victoria H Mann, Sujittra Chaiyadet, Shannon E Karinshak, Banchob Sripa, Neil David Young, Javier Sotillo, Alex Loukas, Paul J Brindley, Thewarach Laha

ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2019

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 o..

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University of Melbourne Researchers

Grants

Awarded by Thailand Research Fund


Awarded by National Health and Medical Research Council


Awarded by National Cancer Institute


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

Thailand Research Fund PHD/0111/2557 Patpicha Arunsan Thewarach LahaNational Health and Medical Research Council APP1109829 Neil David YoungNational Health and Medical Research Council APP1085309 Alex Loukas Javier Sotillo Thewarach LahaNational Cancer Institute R01CA164719 Alex Loukas Thewarach Laha Paul J BrindleyNational Health and Medical Research Council APP1117504 Alex LoukasThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.