Targeting long non-coding RNA to therapeutically upregulate gene expression

Research output: Contribution to journalReview article

312 Scopus citations

Abstract

The majority of currently available drugs and tool compounds exhibit an inhibitory mechanism of action and there is a relative lack of pharmaceutical agents that are capable of increasing the activity of effectors or pathways for therapeutic benefit. Indeed, the upregulation of many genes, including tumour suppressors, growth factors, transcription factors and genes that are deficient in various genetic diseases, would be desired in specific situations. Recently, key roles for regulatory long non-coding RNAs (lncRNAs) in the regulation of gene expression have begun to emerge. lncRNAs can positively or negatively regulate gene expression and chromatin architecture. Here, we review the current understanding of the mechanisms of action of lncRNAs and their roles in disease, focusing on recent work in the design of inhibitors of the natural antisense transcript (NAT) class of lncRNAs, known as antagoNAT oligonucleotides, and the issues associated with their potential therapeutic application.

Original languageEnglish (US)
Pages (from-to)433-446
Number of pages14
JournalNature Reviews Drug Discovery
Volume12
Issue number6
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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