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

Abstract The 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)...

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Autores principales:	Sarah Kadelka, Harel Dahari, Stanca M. Ciupe
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31eebecaa82d4111a962dfeba05e6b78
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spelling	oai:doaj.org-article:31eebecaa82d4111a962dfeba05e6b782021-12-02T15:08:21ZUnderstanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection10.1038/s41598-020-80594-62045-2322https://doaj.org/article/31eebecaa82d4111a962dfeba05e6b782021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80594-6https://doaj.org/toc/2045-2322Abstract The 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.Sarah KadelkaHarel DahariStanca M. CiupeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah Kadelka Harel Dahari Stanca M. Ciupe Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection
description	Abstract The 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.
format	article
author	Sarah Kadelka Harel Dahari Stanca M. Ciupe
author_facet	Sarah Kadelka Harel Dahari Stanca M. Ciupe
author_sort	Sarah Kadelka
title	Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection
title_short	Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection
title_full	Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection
title_fullStr	Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection
title_full_unstemmed	Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection
title_sort	understanding the antiviral effects of rnai-based therapy in hbeag-positive chronic hepatitis b infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/31eebecaa82d4111a962dfeba05e6b78
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Understanding the antiviral effects of RNAi-based therapy in HBeAg-positive chronic hepatitis B infection

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