ArticleNucleic acids research1995
Efficient hammerhead ribozyme-mediated cleavage of the structured hepatitis B virus encapsidation signal in vitro and in cell extracts, but not in intact cells.
Article in Nucleic acids research, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 86 citations in OpenAlex.
- Gene therapeutic approaches to inhibit hepatitis B virus replication.World journal of hepatology · 2015Review
- A Tyr residue in the reverse transcriptase domain can mimic the protein-priming Tyr residue in the terminal protein domain of a hepadnavirus P protein.Journal of virology · 2011Article
- Development of lead hammerhead ribozyme candidates against human rod opsin mRNA for retinal degeneration therapy.Experimental eye research · 2009Article
- Preparation and identification of anti-transforming growth factor beta1 U1 small nuclear RNA chimeric ribozyme in vitro.World journal of gastroenterology · 2003Article
- Targeted ribonuclease can inhibit replication of hepatitis B virus.World journal of gastroenterology · 2003Article
- Development and comparison of procedures for the selection of delta ribozyme cleavage sites within the hepatitis B virus.Nucleic acids research · 2002Article
- Anti-HBV hairpin ribozyme-mediated cleavage of target RNA in vitro.World journal of gastroenterology · 2002Article
- Anti-viral activity of hairpin ribozyme directed against HBV core region in vitro.Journal of Tongji Medical University = Tong ji yi ke da xue xue bao · 2001Article
- Secondary structure prediction and in vitro accessibility of mRNA as tools in the selection of target sites for ribozymes.Nucleic acids research · 2000Article
- Construction of HBV-specific ribozyme and its recombinant with HDV and their cleavage activity in vitro.World journal of gastroenterology · 2000Article
- Intracellular ribozyme-catalyzed trans-cleavage of RNA monitored by fluorescence resonance energy transfer.RNA (New York, N.Y.) · 2000Article
- Combinatorial screening and intracellular antiviral activity of hairpin ribozymes directed against hepatitis B virus.Journal of virology · 1999Article
- A small nucleolar RNA:ribozyme hybrid cleaves a nucleolar RNA target in vivo with near-perfect efficiency.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
- Intracellular RNA cleavage by the hairpin ribozyme.Nucleic acids research · 1998Article
- Antiviral ribozymes. New jobs for ancient molecules.Molecular biotechnology · 1997Review
- Ribozymes. Their functions and strategies for their use.Molecular biotechnology · 1997Review
- The subcellular localization and length of hammerhead ribozymes determine efficacy in human cells.Nucleic acids research · 1997Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV), the causative agent of B-type hepatitis in man, is a small enveloped DNA virus that replicates through reverse transcription of an RNA intermediate, the terminally redundant RNA pregenome. An essential highly conserved cis-element present twice on this RNA is the encapsidation signal epsilon, a stem-loop structure that is critical for pregenome packaging and reverse transcription. Epsilon is hence an attractive target for antiviral therapy. Its structure, however, is a potential obstacle to antivirals whose action depends on hybridization, e.g. ribozymes. Here we demonstrate effective in vitro cleavage inside epsilon by hammerhead ribozymes containing flanking sequences complementary to an adjacent less structured region. Upon co-transfection with a HBV expression construct corresponding ribozymes embedded in a U6 snRNA context led to a significant, though modest, reduction in the steady-state level of HBV pregenomes. Inactive ribozyme mutants revealed that antisense effects contributed substantially to this reduction, however, efficient epsilon cleavage by the intracellularly expressed ribozymes was observed in Mg(2+)-supplemented cell lysates. Artificial HBV pregenomes carrying the ribozymes in cis and model RNAs lacking all HBV sequences except epsilon exhibited essentially the same behaviour. Hence, neither the absence of co-localization of ribozyme and target nor a viral component, but rather a cellular factor(s), is responsible for the strikingly different ribozyme activities inside cells and in cellular extracts.
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