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Publication
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| Title of Article |
Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity |
| Date of Acceptance |
12 December 2018 |
| Journal |
| 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 |
| Author |
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| Reviewing Status |
มีผู้ประเมินอิสระ |
| Status |
ตีพิมพ์แล้ว |
| Level of Publication |
นานาชาติ |
| citation |
true |
| Part of thesis |
true |
| Attach file |
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| Citation |
0
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Journal Publication
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