ArticleProceedings of the National Academy of Sciences of the United States of America2001
RNA-protein hybrid ribozymes that efficiently cleave any mRNA independently of the structure of the target RNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. 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, 80 citations in OpenAlex.
- Review
- Disruption of dengue virus transmission by mosquitoes.Current opinion in insect science · 2015Article
- Methodological obstacles in knocking down small noncoding RNAs.RNA (New York, N.Y.) · 2009Article
- Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome.Virology journal · 2009Article
- Rapid selection of accessible and cleavable sites in RNA by Escherichia coli RNase P and random external guide sequences.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Catalytic nucleic acid enzymes for the study and development of therapies in the central nervous system: Review Article.Gene therapy & molecular biology · 2005Article
- Reversal of HCC drug resistance by using hammerhead ribozymes against multidrug resistance 1 gene.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2005Article
- Effects on RNAi of the tight structure, sequence and position of the targeted region.Nucleic acids research · 2004Article
- Targeting mortalin using conventional and RNA-helicase-coupled hammerhead ribozymes.EMBO reports · 2003Article
- Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells.Nucleic acids research · 2003Article
- A functional gene discovery in the Fas-mediated pathway to apoptosis by analysis of transiently expressed randomized hybrid-ribozyme libraries.Nucleic acids research · 2002Article
- Measurements of weak interactions between truncated substrates and a hammerhead ribozyme by competitive kinetic analyses: implications for the design of new and efficient ribozymes with high sequence specificity.Nucleic acids research · 2002Article
- Identification of genes by hybrid ribozymes that couple cleavage activity with the unwinding activity of an endogenous RNA helicase.EMBO reports · 2002Article
- Identification of genes that function in the TNF-alpha-mediated apoptotic pathway using randomized hybrid ribozyme libraries.Nature biotechnology · 2002Article
- Efficient trans-cleavage by the Schistosoma mansoni SMalpha1 hammerhead ribozyme in the extreme thermophile Thermus thermophilus.Nucleic acids research · 2002Article
- Significantly higher activity of a cytoplasmic hammerhead ribozyme than a corresponding nuclear counterpart: engineered tRNAs with an extended 3' end can be exported efficiently and specifically to the cytoplasm in mammalian cells.Nucleic acids research · 2001Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ribozyme activity in vivo depends on achieving high-level expression, intracellular stability, target colocalization, and cleavage site access. At present, target site selection is problematic because of unforeseeable secondary and tertiary RNA structures that prevent cleavage. To overcome this design obstacle, we wished to engineer a ribozyme that could access any chosen site. To create this ribozyme, the constitutive transport element (CTE), an RNA motif that has the ability to interact with intracellular RNA helicases, was attached to our ribozymes so that the helicase-bound, hybrid ribozymes would be produced in cells. This modification significantly enhanced ribozyme activity in vivo, permitting cleavage of sites previously found to be inaccessible. To confer cleavage enhancement, the CTE must retain helicase-binding activity. Binding experiments demonstrated the likely involvement of RNA helicase(s). We found that attachment of the RNA motif to our tRNA ribozymes leads to cleavage in vivo at the chosen target site regardless of the local RNA secondary or tertiary structure.
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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.