Targeting Long Noncoding RNA with Antisense Oligonucleotide Technology as Cancer Therapeutics

  • Tianyuan ZhouEmail author
  • Youngsoo Kim
  • A. Robert MacLeod
Part of the Methods in Molecular Biology book series (MIMB, volume 1402)


Recent annotation of the human transcriptome revealed that only 2 % of the genome encodes proteins while the majority of human genome is transcribed into noncoding RNAs. Although we are just beginning to understand the diverse roles long noncoding RNAs (lncRNAs) play in molecular and cellular processes, they have potentially important roles in human development and pathophysiology. However, targeting of RNA by traditional structure-based design of small molecule inhibitors has been difficult, due to a lack of understanding of the dynamic tertiary structures most RNA molecules adopt. Antisense oligonucleotides (ASOs) are capable of targeting specific genes or transcripts directly through Watson–Crick base pairing and thus can be designed based on sequence information alone. These agents have made possible specific targeting of “non-druggable targets” including RNA molecules. Here we describe how ASOs can be applied in preclinical studies to reduce levels of lncRNAs of interest.

Key words

Antisense oligonucleotide Control ASO Non-druggable targets Off-target RNA therapeutics Target reduction RNase H qRT-PCR Transfection Free uptake 



We thank XueHai Liang for discussion and sharing unpublished data. We are grateful to Lauren Elder for editorial assistance.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Tianyuan Zhou
    • 1
    Email author
  • Youngsoo Kim
    • 1
  • A. Robert MacLeod
    • 1
  1. 1.Antisense Drug Discovery, OncologyIsis Pharmaceuticals, IncCarlsbadUSA

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