The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Silencing of microRNA families by seed-targeting tiny LNAs
Open accessAbstract
The challenge of understanding the widespread biological roles of animal microRNAs (miRNAs) has prompted the development of genetic and functional genomics technologies for miRNA loss-of-function studies. However, tools for exploring the functions of entire miRNA families are still limited. We developed a method that enables antagonism of miRNA function using seed-targeting 8-mer locked nucleic acid (LNA) oligonucleotides, termed tiny LNAs. Transfection of tiny LNAs into cells resulted in simultaneous inhibition of miRNAs within families sharing the same seed with concomitant upregulation of direct targets. In addition, systemically delivered, unconjugated tiny LNAs showed uptake in many normal tissues and in breast tumors in mice, coinciding with long-term miRNA silencing. Transcriptional and proteomic profiling suggested that tiny LNAs have negligible off-target effects, not significantly altering the output from mRNAs with perfect tiny LNA complementary sites. Considered together, these data support the utility of tiny LNAs in elucidating the functions of miRNA families in vivo.
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Cites
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Self-citationSilencing of microRNAs in vivo with ‘antagomirs’
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“Prediction of targets by identifying conserved seed sites in mammalian 3′ UTRs or by analysis of transcriptional profiles and proteomic data supports the notion that miRNAs may regulate a large fraction of all protein-coding gene”
BackgroundmiR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
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Self-citationmiR‐21: a small multi‐faceted RNA
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LNA (Locked Nucleic Acid): High-Affinity Targeting of Complementary RNA and DNA
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Most Caenorhabditis elegans microRNAs Are Individually Not Essential for Development or Viability
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Cited by
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MicroRNAs in Stress Signaling and Human Disease
Mendell, J. T., & Olson, E. N. (2012) · Cell · doi:10.1016/j.cell.2012.02.005 · Cited by 1,673
Noncoding RNA therapeutics—Challenges and potential solutions
Winkle, M., El-Daly, S. M., Fabbri, M., & Calin, G. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00219-z · Cited by 1,551
Diverse Applications of Nanomedicine
Pelaz, B., Alexiou, C., Alvarez-Puebla, R. A., Alves, F., Andrews, A. M., Ashraf, S., Balogh, L. P., Ballerini, L., Bestetti, A., Brendel, C., et al. (2017) · ACS Nano · doi:10.1021/acsnano.6b06040 · Cited by 1,350
The chemical evolution of oligonucleotide therapies of clinical utility
Khvorova, A., & Watts, J. K. (2017) · Nature Biotechnology · doi:10.1038/nbt.3765 · Cited by 1,216
Metadata
- Authors
- Obad, S., dos Santos, C. O., Petri, A., Heidenblad, M., Broom, O., Ruse, C., Fu, C., Lindow, M., Stenvang, J., Straarup, E. M., Hansen, H. F., Koch, T., Pappin, D., Hannon, G. J., & Kauppinen, S.
- Venue
- Nature Genetics
- Published
- 2011-03-20
- Volume
- 43
- Issue
- 4
- Pages
- 371-378
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2133814931
- Cited by
- 627
- References
- 11
- FWCI
- 31.62
- Type
- journal article
- Language
- en
- Open access
- green
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