ArticleNucleic acids research2009
RNA polymerase III can drive polycistronic expression of functional interfering RNAs designed to resemble microRNAs.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- miR-AB, a miRNA-based shRNA viral toolkit for multicolor-barcoded multiplex RNAi at a single-cell level.EMBO reports · 2022Article
- A simplified system for the effective expression and delivery of functional mature microRNAs in mammalian cells.Cancer gene therapy · 2020Article
- RNA Interference Therapies for an HIV-1 Functional Cure.Viruses · 2017Review
- Bone Marrow Gene Therapy for HIV/AIDS.Viruses · 2015Review
- MicroRNAs: an emerging science in cancer epigenetics.Journal of clinical bioinformatics · 2013Article
- MicroRNA-mediated drug resistance in breast cancer.Clinical epigenetics · 2011Article
- Creating a flexible multiple microRNA expression vector by linking precursor microRNAs.Biochemical and biophysical research communications · 2011Article
- Article
- Transcriptional regulation of mammalian miRNA genes.Genomics · 2011Review
- Improved siRNA/shRNA functionality by mismatched duplex.PloS one · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
In both research and therapeutic applications of RNA interference, it is often advantageous to silence several targets simultaneously. Toward this end, several groups have developed vectors that utilize the model of endogenously encoded micro (mi) RNAs, where a single RNA polymerase II promoter can drive the expression of multiple interfering RNAs. Stronger pol III promoters have been used to drive individual short hairpin (sh) RNAs, but to date, it has been necessary to repeat the promoter in each silencing cassette to achieve multiplexed expression from a single vector. Here, we show that it is possible to drive polycistronic expression from a single pol III promoter when the interfering RNAs are formatted to resemble miRNAs rather than shRNAs. As many as four miRNAs designed to target hepatitis B virus (HBV) transcripts are shown to be processed and functional in reporter assays as well as in the context of replicating virus in cell culture systems. Although it has been observed that high levels of expression of shRNAs can lead to cytotoxicity, we find no significant evidence in transient transfection assays that the HBV-miRNAs produced by our vectors compete for the activity of endogenously produced miR-122 or for processing of an exogenously expressed miR-EGFP.
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Registered trials
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.