ArticleMolecular therapy. Nucleic acids2017
Nucleic Acid Polymers with Accelerated Plasma and Tissue Clearance for Chronic Hepatitis B Therapy.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- HBV serum RNA kinetics during nucleic acid polymers based therapy predict functional cure.Antiviral research · 2025Trial
- Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases.Biomolecules · 2025Review
- [Research progress on novel antiviral therapeutic drugs for chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Review
- Novel Approaches to Inhibition of HBsAg Expression from cccDNA and Chromosomal Integrants: A Review.Journal of clinical and translational hepatology · 2023Review
- Pangenomic antiviral effect of REP 2139 in CRISPR/Cas9 engineered cell lines expressing hepatitis B virus surface antigen.PloS one · 2023Article
- Oligonucleotide-Based Therapies for Chronic HBV Infection: A Primer on Biochemistry, Mechanisms and Antiviral Effects.Viruses · 2022Review
- Novel Neplanocin A Derivatives as Selective Inhibitors of Hepatitis B Virus with a Unique Mechanism of Action.Antimicrobial agents and chemotherapy · 2022Article
- Editorial:Molecular therapy. Nucleic acids · 2022Article
- Innate and adaptive immune escape mechanisms of hepatitis B virus.World journal of gastroenterology · 2022Review
- The evolution and clinical impact of hepatitis B virus genome diversity.Nature reviews. Gastroenterology & hepatology · 2020Review
- New Approaches to the Treatment of Chronic Hepatitis B.Journal of clinical medicine · 2020Review
- Modelling hepatitis D virus RNA and HBsAg dynamics during nucleic acid polymer monotherapy suggest rapid turnover of HBsAg.Scientific reports · 2020Article
- Review
- Development of Direct-acting Antiviral and Host-targeting Agents for Treatment of Hepatitis B Virus Infection.Gastroenterology · 2019Review
- Nucleic acid polymer REP 2139 and nucleos(T)ide analogues act synergistically against chronic hepadnaviral infection in vivo in Pekin ducks.Hepatology (Baltimore, Md.) · 2018Article
- Activity of nucleic acid polymers in rodent models of HBV infection.Antiviral research · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
REP 2139 is a nucleic acid polymer (NAP) currently under clinical development for chronic hepatitis B (HBV) therapy. This preclinical study investigated different REP 2139 analogs that would display reduced accumulation in the serum and tissues, while retaining an antiviral effect against HBV infection. REP 2139 analogs were evaluated in human plasma, CD-1 mice, cynomolgus monkeys, and Pekin ducks. Discrete ribose transformation to 2'OH in selected riboadenosines resulted in a slow degradation in acidified human plasma that plateaued after 48 hr. REP 2165, a REP 2139 analog containing three unmodified riboadenosines equally spaced throughout the polymer, showed similar plasma clearance and tissue distribution as REP 2139 in mice and cynomolgus monkeys after a single dose. Interestingly, after repeated administration, accumulation of REP 2165 in plasma and organs was reduced, indicating a dramatically faster rate of clearance from organs after therapy was ended in both species. Both REP 2139 and REP 2165 were well tolerated at clinically relevant doses, with no alterations in liver, kidney, or hematological function. In chronic duck HBV (DHBV) infection, REP 2165 displayed significantly reduced liver accumulation after repeated dosing but retained antiviral activity similar to REP 2139. These results indicate the therapeutic potential of REP 2165 against chronic HBV infection in patients is similar to REP 2139, but with significantly reduced drug accumulation and improved tissue clearance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.