Therapeutic Targeting of RIG-I and MDA5 Might Not Lead to the Same Rome

Trends Pharmacol Sci. 2019 Feb;40(2):116-127. doi: 10.1016/ Epub 2018 Dec 31.


RIG-I and MDA5 receptors are key sensors of pathogen-associated molecular pattern (PAMP)-containing viral RNA and transduce downstream signals to activate an antiviral and immunomodulatory response. Fifteen years of research have put them at the center of an ongoing hunt for novel pharmacological pan-antivirals, vaccine adjuvants, and antitumor strategies. Current knowledge testifies to the redundant, but also distinct, functions mediated by RIG-I and MDA5, opening opportunities for the use of specific and potent nucleic acid agonists. We critically discuss the evidence and remaining knowledge gaps that have an impact on the choice and design of optimal RNA ligands to achieve an appropriate immunostimulatory response, with limited adverse effects, for prophylactic and therapeutic interventions against viruses and cancer in humans.

Keywords: MDA5; RIG-I; antiviral; cancer; immunotherapy; vaccine.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antiviral Agents / pharmacology
  • Autoimmune Diseases / drug therapy
  • DEAD Box Protein 58 / chemistry
  • DEAD Box Protein 58 / immunology
  • DEAD Box Protein 58 / metabolism*
  • Humans
  • Interferon-Induced Helicase, IFIH1 / chemistry
  • Interferon-Induced Helicase, IFIH1 / immunology
  • Interferon-Induced Helicase, IFIH1 / metabolism*
  • Ligands
  • Molecular Targeted Therapy
  • Pathogen-Associated Molecular Pattern Molecules / immunology
  • Pathogen-Associated Molecular Pattern Molecules / metabolism


  • Adjuvants, Immunologic
  • Antiviral Agents
  • Ligands
  • Pathogen-Associated Molecular Pattern Molecules
  • DEAD Box Protein 58
  • Interferon-Induced Helicase, IFIH1