Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection

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dc.contributor.authorKadelka, Sarahen
dc.contributor.authorDahari, Harelen
dc.contributor.authorCiupe, Stanca M.en
dc.contributor.departmentMathematicsen
dc.date.accessioned2021-06-07T18:37:05Zen
dc.date.available2021-06-07T18:37:05Zen
dc.date.issued2021-01-08en
dc.description.abstractThe RNA interference (RNAi) drug ARC-520 was shown to be effective in reducing serum hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in HBeAg-positive patients treated with a single dose of ARC-520 and daily nucleosidic analogue (entecavir). To provide insights into HBV dynamics under ARC-520 treatment and its efficacy in blocking HBV DNA, HBsAg, and HBeAg production we developed a multi-compartmental pharmacokinetic-pharamacodynamic model and calibrated it with frequent measured HBV kinetic data. We showed that the time-dependent single dose ARC-520 efficacies in blocking HBsAg and HBeAg are more than 96% effective around day 1, and slowly wane to 50% in 1-4 months. The combined single dose ARC-520 and entecavir effect on HBV DNA was constant over time, with efficacy of more than 99.8%. The observed continuous HBV DNA decline is entecavir mediated, the strong but transient HBsAg and HBeAg decays are ARC-520 mediated. The modeling framework may help assess ongoing RNAi drug development for hepatitis B virus infection.en
dc.description.notesSK and SMC acknowledge funding from National Science Foundation Grant No. 1813011. HD acknowledges funding from NIH Grant Nos. R01AI144112 and R01AI146917. We thank Christine Wooddell and the anonymous reviewers for their valuable comments.en
dc.description.sponsorshipNational Science FoundationNational Science Foundation (NSF) [1813011]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AI144112, R01AI146917]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-020-80594-6en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.other200en
dc.identifier.pmid33420293en
dc.identifier.urihttp://hdl.handle.net/10919/103656en
dc.identifier.volume11en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleUnderstanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infectionen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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