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Replicor提供以上研究的材料.研究人员中包括来自Replicor的Dr A. Vaillant (首席科学官).
结论:
We therefore hypothesize that the antiviral activity of NAPs optimized to treat HBV infection in patients cannot be explained by direct induction of innate antiviral responses.
"因此，我们假设优化用于治疗患者HBV感染的NAP的抗病毒活性不能通过直接诱导先天抗病毒反应来解释。"
Sci Rep. 2017 Mar 8;7:43838. doi: 10.1038/srep43838.
Nucleic acid-based polymers effective against hepatitis B Virus infection in patients don't harbor immunostimulatory properties in primary isolated liver cells.
Real CI1,2, Werner M1, Paul A2, Gerken G1, Schlaak JF1,3, Vaillant A4, Broering R1.
Author information
1
Department of Gastroenterology and Hepatology, University Hospital at the University Duisburg-Essen, Essen, Germany.
2
Department of General-, Visceral- and Transplantation Surgery, University Hospital at the University Duisburg-Essen, Essen, Germany.
3
Evangelisches Klinikum Niederrhein GmbH, Duisburg, Germany.
4
Replicor Inc., Montreal, Quebec, Canada.
Abstract
Nucleic acid polymers (NAPs) block the release of subviral particles from hepatocytes, a mechanism consistent with their antiviral activity against hepatitis B virus (HBV) in patients. Analysis of immunostimulatory properties of NAPs were conducted with several NAP species: REP 2006, the prototypic degenerate NAP [dN]40, containing TLR9-stimulatory CpG; REP 2055 a clinically active NAP with a sequence [dAdC]20 devoid of CpG content; REP 2139 (also clinically active) and REP 2165 (REP 2055 analogues further rendered immunologically inactive by replacing cytidine with 5-methylcytidine and incorporating 2'-O methylation of riboses). These analyses revealed pro-inflammatory responses in human peripheral blood mononuclear cells with REP 2006 and with REP 2139 and REP 2165 only at high dose but displayed no significant antiviral activity. In primary isolated human hepatocytes and liver sinusoidal endothelial cells no significant inflammatory or antiviral responses were detected for any NAPs. In human Kupffer cells pro-inflammatory activity was observed with REP 2006 and REP 2055, whereas a weak but significant induction of interferon genes was only observed with REP 2006 at the highest concentration. We therefore hypothesize that the antiviral activity of NAPs optimized to treat HBV infection in patients cannot be explained by direct induction of innate antiviral responses.
PMID:
28272460
PMCID:
PMC5341074
DOI:
10.1038/srep43838
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发表于 2019-3-9 20:40
