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Trends Pharmacol Sci. 2019 Feb;40(2):116-127. doi: 10.1016/j.tips.2018.12.003. Epub 2018 Dec 31.

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

Author information

1
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada; Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
2
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada; Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada. Electronic address: nathalie.grandvaux@umontreal.ca.

Abstract

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

PMID:
30606502
DOI:
10.1016/j.tips.2018.12.003
[Indexed for MEDLINE]

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