The notorious R.N.A. in the spotlight - drug or target for the treatment of disease

RNA Biol. 2017 May 4;14(5):651-668. doi: 10.1080/15476286.2016.1208323. Epub 2016 Jul 14.

Abstract

mRNA is an attractive drug target for therapeutic interventions. In this review we highlight the current state, clinical trials, and developments in antisense therapy, including the classical approaches like RNaseH-dependent oligomers, splice-switching oligomers, aptamers, and therapeutic RNA interference. Furthermore, we provide an overview on emerging concepts for using RNA in therapeutic settings including protein replacement by in-vitro-transcribed mRNAs, mRNA as vaccines and anti-allergic drugs. Finally, we give a brief outlook on early-stage RNA repair approaches that apply endogenous or engineered proteins in combination with short RNAs or chemically stabilized oligomers for the re-programming of point mutations, RNA modifications, and frame shift mutations directly on the endogenous mRNA.

Keywords: Antisense oligonucleotide; RNA interference; RNA repair; RNA vaccines; chemically modified oligonucleotides; genetic disease; site-directed RNA editing; splice-switching oligonucleotide; therapeutic aptamer; therapeutic mRNA.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / metabolism
  • Clinical Trials as Topic
  • Drug Discovery
  • Genetic Diseases, Inborn / therapy*
  • Humans
  • Oligonucleotides, Antisense / therapeutic use
  • RNA Editing
  • RNA Interference
  • RNA Stability*
  • RNA, Antisense / therapeutic use*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNAi Therapeutics*
  • Ribonuclease H / metabolism*

Substances

  • Aptamers, Nucleotide
  • Oligonucleotides, Antisense
  • RNA, Antisense
  • RNA, Messenger
  • Ribonuclease H