ArticleNucleic acids research1997
The subcellular localization and length of hammerhead ribozymes determine efficacy in human cells.
Article in Nucleic acids research, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 63 citations in OpenAlex.
- Ex vivo rescue of recombinant very virulent IBDV using a RNA polymerase II driven system and primary chicken bursal cells.Scientific reports · 2020Article
- A cellular high-throughput screening approach for therapeutic trans-cleaving ribozymes and RNAi against arbitrary mRNA disease targets.Experimental eye research · 2016Article
- Variables and strategies in development of therapeutic post-transcriptional gene silencing agents.Journal of ophthalmology · 2011Article
- Development of lead hammerhead ribozyme candidates against human rod opsin mRNA for retinal degeneration therapy.Experimental eye research · 2009Article
- Hitting bacteria at the heart of the central dogma: sequence-specific inhibition.Microbial cell factories · 2007Article
- Free energy landscapes of RNA/RNA complexes: with applications to snRNA complexes in spliceosomes.Journal of molecular biology · 2006Article
- Design of a ribozyme targeting human telomerase reverse transcriptase and cloning of it's gene.World journal of gastroenterology · 2003Article
- TIF1beta functions as a coactivator for C/EBPbeta and is required for induced differentiation in the myelomonocytic cell line U937.Genes & development · 2001Article
- HIV-1 LTR as a target for synthetic ribozyme-mediated inhibition of gene expression: site selection and inhibition in cell culture.Nucleic acids research · 2000Article
- Theoretical design of antisense genes with statistically increased efficacy.Nucleic acids research · 2000Article
- Inhibition of luciferase expression by synthetic hammerhead ribozymes and their cellular uptake.Nucleic acids research · 1999Article
- Hammerhead ribozyme kinetics.RNA (New York, N.Y.) · 1998Review
- A spermidine-induced conformational change of long-armed hammerhead ribozymes: ionic requirements for fast cleavage kinetics.Nucleic acids research · 1997Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The length requirements of the antisense portion of hammerhead ribozymes for efficacy in living cells was investigated. The HIV-1tat-directed asymmetric hammerhead ribozyme alphaYRz195 was used with a 195 nt 3'-antisense arm and a 3 nt 5'-antisense portion as well as a set of successively 3'-shortened derivatives thereof. In the 3'-antisense arm a minimum length of 20 complementary nucleotides was required for efficient association with a 645 nt target RNA transcript in vitro(for all constructs kass ranged between 0.3 and 1.8x104/M/s). The cleavage rate constants (kcleav) were independent of the length of the antisense flank and ranged between 0.8 and 1.2x10-4/s. However, the length of the antisense arms, as well as the mode of delivery and the subcellular location of the ribozymes, had a dramatic effect on efficacy in HIV-1-producing human cells. When proviral HIV-1 DNA and ribozymes were co-microinjected into the nucleus of human cells, a minimum length of 51 nt in the antisense arm was necessary for antisense- and ribozyme-mediated inhibition of HIV-1 replication. Ribozymes with shorter antisense arms were almost ineffective. Conversely, short chain ribozymes, including those with chemical modifications, were superior to long chain ribozymes when co-microinjected into the cytoplasm. When transfected, all ribozymes showed an antisense effect as well as an additional ribozyme-mediated increase in inhibition. Consequences for the design and application of ribozymes are discussed.
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