Knockdown of Circular RNAs Using LNA-Modified Antisense Oligonucleotides

Marianne Bengtson Løvendorf, Anja Holm, Andreas Petri, Charlotte Albæk Thrue, Shizuka Uchida, Morten T. Venø, Sakari Kauppinen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Circular RNAs (circRNAs) constitute an abundant class of covalently closed noncoding RNA molecules that are formed by backsplicing from eukaryotic protein-coding genes. Recent studies have shown that circRNAs can act as microRNA or protein decoys, as well as transcriptional regulators. However, the functions of most circRNAs are still poorly understood. Because circRNA sequences overlap with their linear parent transcripts, depleting specific circRNAs without affecting host gene expression remains a challenge. In this study, we assessed the utility of LNA-modified antisense oligonucleotides (ASOs) to knock down circRNAs for loss-of-function studies. We found that, while most RNase H-dependent gapmer ASOs mediate effective knockdown of their target circRNAs, some gapmers reduce the levels of the linear parent transcript. The circRNA targeting specificity can be enhanced using design-optimized gapmer ASOs, which display potent and specific circRNA knockdown with a minimal effect on the host genes. In summary, our results demonstrate that LNA-modified ASOs complementary to backsplice-junction sequences mediate robust knockdown of circRNAs in vitro and, thus, represent a useful tool to explore the biological roles of circRNAs in loss-of-function studies in cultured cells and animal models.
Original languageEnglish
JournalNucleic Acid Therapeutics
Issue number1
Pages (from-to)45-57
Number of pages13
Publication statusPublished - 1 Jan 2023

Bibliographical note

PMID: 36445751


  • antisense oligonucleotide
  • circRNAs
  • knockdown
  • locked nucleic acid


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