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Cited by 422RNA Interference and Gene DeliveryMicroRNA in disease regulationDNA and Nucleic Acid Chemistry

Improved targeting of miRNA with antisense oligonucleotides

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Davis, S.·2006·Nucleic Acids Research
DOI 10.1093/nar/gkl183PMC PMC1459537
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Abstract

MicroRNAs (miRNAs) are a class of 20-24 nt noncoding RNAs that regulate target mRNAs post-transcriptionally by binding with imperfect complementarity in the 3'-untranslated region (3'-UTR) and inhibiting translation or RNA stability. Current understanding of miRNA biology is limited, and antisense oligonucleotide (ASO) inhibition is a powerful technique for miRNA functionalization in vitro and in vivo, and for therapeutic targeting of miRNAs. Identification of optimal ASO chemistries for targeting miRNAs is therefore of great interest. We evaluated a number of 2'-sugar and backbone ASO modifications for their ability to inhibit miR-21 activity on a luciferase reporter mRNA. ASO modifications that improved target affinity improved miRNA ASO activity, yet the positioning of high-affinity modifications also had dramatically different effects on miRNA activity, suggesting that more than affinity determined the effectiveness of the miRNA ASOs. We present data in which the activity of a modified miRNA ASO was inversely correlated to its tolerability as an siRNA passenger strand, suggesting that a similar mechanism could be involved in the dissociation of miRNA ASOs and siRNA passenger strands. These studies begin to define the factors important for designing improved miRNA ASOs, enabling more effective miRNA functionalization and therapeutic targeting.

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  • The 2'-O-MOE ASO was the most potent in repressing miR-21 activity among molecules tested.

    “Among the molecules tested, the 2′-O-MOE ASO was the most potent in repressing miR-21 activity (Fig. 2A), in agreement with previous data (10), whereas the uniform 2′-O-methyl ASO was the least potent, and mixed locked nucleic acid (LNA)-DNA oligonucleotides were variable (data not shown).”

    From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [10]

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Cited by

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Authors
Davis, S.
Affiliations
Ionis Pharmaceuticals (United States) (US)
Corresponding author
Davis, S.
ORCID
Davis, S.
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2006-04-28
Volume
34
Issue
8
Pages
2294-2304
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkl183
PMC
PMC1459537
OpenAlex
W2104905829
Cited by
422
References
1
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FWCI
9.25
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Nucleic Acids Research (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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 › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
microRNA, antisense oligonucleotides, miR-21, backbone modification, 3' untranslated region, post-transcriptional regulation, oligonucleotide design
MeSH terms
Carbohydrates, HeLa Cells, Humans, Kinetics, Phosphates, Oligonucleotides, Antisense, Genes, Reporter, Base Pair Mismatch, RNA Interference, MicroRNAs

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