Targeting noncoding RNAs in disease

J Clin Invest. 2017 Mar 1;127(3):761-771. doi: 10.1172/JCI84424. Epub 2017 Mar 1.


Many RNA species have been identified as important players in the development of chronic diseases, including cancer. Over the past decade, numerous studies have highlighted how regulatory RNAs such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play crucial roles in the development of a disease state. It is clear that the aberrant expression of miRNAs promotes tumor initiation and progression, is linked with cardiac dysfunction, allows for the improper physiological response in maintaining glucose and insulin levels, and can prevent the appropriate integration of neuronal networks, resulting in neurodegenerative disorders. Because of this, there has been a major effort to therapeutically target these noncoding RNAs. In just the past 5 years, over 100 antisense oligonucleotide-based therapies have been tested in phase I clinical trials, a quarter of which have reached phase II/III. Most notable are fomivirsen and mipomersen, which have received FDA approval to treat cytomegalovirus retinitis and high blood cholesterol, respectively. The continued improvement of innovative RNA modifications and delivery entities, such as nanoparticles, will aid in the development of future RNA-based therapeutics for a broader range of chronic diseases. Here we summarize the latest promises and challenges of targeting noncoding RNAs in disease.

Publication types

  • Review

MeSH terms

  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Cytomegalovirus Retinitis* / drug therapy
  • Cytomegalovirus Retinitis* / genetics
  • Cytomegalovirus Retinitis* / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs* / antagonists & inhibitors
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / genetics
  • Neurodegenerative Diseases* / metabolism
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Oligodeoxyribonucleotides, Antisense / therapeutic use*
  • RNA, Long Noncoding* / antagonists & inhibitors
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Neoplasm* / antagonists & inhibitors
  • RNA, Neoplasm* / genetics
  • RNA, Neoplasm* / metabolism


  • MicroRNAs
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Long Noncoding
  • RNA, Neoplasm