Managing MicroRNAs with Vector-Encoded Decoy-Type Inhibitors
Open accessAbstract
A rapidly growing understanding of the complex circuitry of microRNA (miRNA)-mediated gene regulation is attracting attention to miRNAs as new drug targets. Targeted miRNA suppression is achieved in a sequence-specific manner by antisense RNA "decoy" molecules. Such synthetic miRNA inhibitors have reached the clinic with remarkable pace and may soon appear as new therapeutic modalities in several diseases. Shortcomings, however, include high production costs, the requirement for repeated administration, and difficulty achieving tissue-specific delivery. With the many recent landmark achievements in clinical gene therapy, new and refined vector-encoded miRNA suppression technologies are attractive for many applications, not least as tools in innumerable daily studies of miRNA biology in laboratories worldwide. Here, we provide an overview of the strategies that have been used to adapt vector-encoded inhibitors for miRNA suppression and discuss advantages related to spatiotemporal and long-term miRNA attenuation. With the remarkable new discovery of miRNA management by naturally occurring circular RNAs, RNA circles generated by trans-splicing mechanisms may prove to be well-suited carriers of decoy-type miRNA inhibitors. The community will aspire to combine circles with high-affinity miRNA decoy methodologies, and such "vectorized" RNA circles may represent new solid ways to deliver miRNA inhibitors, perhaps even with therapeutic applications.
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Sponge constructs are designed to bind complementary miRNA(s) or their seed sequences, and hence block the binding of the miRNA to its biological targets.
“The sponge construct are designed to bind its complementary miRNA(s) or their seed sequences, and hence block the binding of the miRNA to its biological targets (29–31).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [29]
miRNA inhibition using decoy or sponge-like constructs has potential therapeutic benefit.
“It has already been shown that miRNA inhibition using decoy or sponge-like constructs have a potential therapeutic benefit.”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [29]
Using decoy or sponge-like constructs for miRNA inhibition has been shown to bind complementary miRNA(s) or their seed sequences and block their effects.
“Using decoy or sponge-like constructs for miRNA inhibition have been already shown before with good effect in binding to its complementary miRNA(s) or their seed sequences and blocking their effects (29–31, 56, 57).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [29]
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- Authors
- Bak, R. O., Hollensen, A. K., & Mikkelsen, J. G.
- Affiliations
- Aarhus University (DK)
- Corresponding author
- Mikkelsen, Jacob Giehm
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 21
- Issue
- 8
- Pages
- 1478-1485
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3734669
- OpenAlex
- W2061731661
- Cited by
- 49
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 2
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Aase og Ejnar Danielsens Fond
- Lundbeckfonden
- Aarhus Universitet
- Agnes og Poul Friis Fond
- Novo Nordisk Fonden
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- microRNA, trans-splicing, microRNA delivery, gene therapy vectors, tissue-specific delivery
- MeSH terms
- RNA, Circular, Animals, Gene Expression Regulation, Genetic Vectors, Humans, Organ Specificity, RNA, Genetic Therapy, RNA, Antisense, Gene Transfer Techniques, Trans-Splicing, RNA Interference, MicroRNAs
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