Evading innate immunity in nonviral mRNA delivery: don't shoot the messenger

Joke Devoldere; Heleen Dewitte; Stefaan C De Smedt; Katrien Remaut

doi:10.1016/j.drudis.2015.07.009

Evading innate immunity in nonviral mRNA delivery: don't shoot the messenger

Drug Discov Today. 2016 Jan;21(1):11-25. doi: 10.1016/j.drudis.2015.07.009. Epub 2015 Jul 23.

Authors

Joke Devoldere¹, Heleen Dewitte¹, Stefaan C De Smedt¹, Katrien Remaut²

Affiliations

¹ Laboratory for General Biochemistry and Physical Pharmacy, Department of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
² Laboratory for General Biochemistry and Physical Pharmacy, Department of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: Katrien.Remaut@UGent.be.

PMID: 26210957
DOI: 10.1016/j.drudis.2015.07.009

Abstract

In the field of nonviral gene therapy, in vitro transcribed (IVT) mRNA has emerged as a promising tool for the delivery of genetic information. Over the past few years it has become widely known that the introduction of IVT mRNA into mammalian cells elicits an innate immune response that has favored mRNA use toward immunotherapeutic vaccination strategies. However, for non-immunotherapy-related applications this intrinsic immune-stimulatory activity directly interferes with the aimed therapeutic outcome, because it can seriously compromise the expression of the desired protein. This review presents an overview of the immune-related obstacles that limit mRNA advance for non-immunotherapy-related applications.

Publication types

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

MeSH terms

Animals
Genetic Therapy / methods
Humans
Immunity, Innate / genetics*
Immunity, Innate / immunology*
Immunotherapy / methods
RNA, Messenger / genetics*
RNA, Messenger / immunology*

Substances

RNA, Messenger