ArticleMolecular therapy. Nucleic acids2014
Optimization of Critical Hairpin Features Allows miRNA-based Gene Knockdown Upon Single-copy Transduction.
Article in Molecular therapy. Nucleic acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
- Multiplex engineering using microRNA-mediated gene silencing in CAR T cells.Frontiers in immunology · 2025Article
- Stable overexpression of native and artificial miRNAs for the production of differentially fucosylated antibodies in CHO cells.Engineering in life sciences · 2024Article
- Arylsulfatases and neuraminidases modulate engagement of CCR5 by chemokines by removing key electrostatic interactions.Scientific reports · 2024Article
- Efficient shRNA-based knockdown of multiple target genes for cell therapy using a chimeric miRNA cluster platform.Molecular therapy. Nucleic acids · 2023Article
- Identification of a miRNA multi-targeting therapeutic strategy in glioblastoma.Cell death & disease · 2023Article
- Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex.Development (Cambridge, England) · 2020Article
- Optimizing Synthetic miRNA Minigene Architecture for Efficient miRNA Hairpin Concatenation and Multi-target Gene Knockdown.Molecular therapy. Nucleic acids · 2019Article
- Inactivating hepatic follistatin alleviates hyperglycemia.Nature medicine · 2018Article
- Article
- Perturbed Wnt signaling leads to neuronal migration delay, altered interhemispheric connections and impaired social behavior.Nature communications · 2017Article
- Improved knockdown from artificial microRNAs in an enhanced miR-155 backbone: a designer's guide to potent multi-target RNAi.Nucleic acids research · 2016Article
- Multilineage polyclonal engraftment of Cal-1 gene-modified cells and in vivo selection after SHIV infection in a nonhuman primate model of AIDS.Molecular therapy. Methods & clinical development · 2016Article
- ChREBP Regulates Itself and Metabolic Genes Implicated in Lipid Accumulation in β-Cell Line.PloS one · 2016Article
- Lentivector Knockdown of CCR5 in Hematopoietic Stem and Progenitor Cells Confers Functional and Persistent HIV-1 Resistance in Humanized Mice.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene knockdown using micro RNA (miRNA)-based vector constructs is likely to become a prominent gene therapy approach. It was the aim of this study to improve the efficiency of gene knockdown through optimizing the structure of miRNA mimics. Knockdown of two target genes was analyzed: CCR5 and green fluorescent protein. We describe here a novel and optimized miRNA mimic design called mirGE comprising a lower stem length of 13 base pairs (bp), positioning of the targeting strand on the 5' side of the miRNA, together with nucleotide mismatches in upper stem positions 1 and 12 placed on the passenger strand. Our mirGE proved superior to miR-30 in four aspects: yield of targeting strand incorporation into RNA-induced silencing complex (RISC); incorporation into RISC of correct targeting strand; precision of cleavage by Drosha; and ratio of targeting strand over passenger strand. A triple mirGE hairpin cassette targeting CCR5 was constructed. It allowed CCR5 knockdown with an efficiency of over 90% upon single-copy transduction. Importantly, single-copy expression of this construct rendered transduced target cells, including primary human macrophages, resistant to infection with a CCR5-tropic strain of HIV. Our results provide new insights for a better knockdown efficiency of constructs containing miRNA. Our results also provide the proof-of-principle that cells can be rendered HIV resistant through single-copy vector transduction, rendering this approach more compatible with clinical applications.
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Registered trials
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