The DOI matches its Crossref record; 149 of the 150 references it cites were found in a registry or an index.
Evading innate immunity in nonviral mRNA delivery: don't shoot the messenger.
Open accessAbstract
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.
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“however, antigen non-specific stimulation of type I interferon pathways has been demonstrated with other formulations of mRNA in animal models78,79.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [79]
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“Uridine-containing mRNA stimulates the innate immune response and has an established adjuvant function when used as a vaccine.34,35”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [34]
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“These limitations are based on the intrinsic immunogenicity of unmodified mRNA due to intracellular detection131,132 and type I interferon (IFN) production,34 which in turn is responsible for the inhibition of translation, the reduction of CD8+ T cell activation, and the inhibition of T helper cell generation.”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [34]
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Metadata
- Authors
- Devoldere, J., Dewitte, H., De Smedt, S. C., & Remaut, K.
- Affiliations
- Ghent University (BE)
- Corresponding author
- Remaut, Katrien
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 21
- Issue
- 1
- Pages
- 11-25
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W1529085705
- Cited by
- 112
- References
- 150
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 10 · 2023: 9 · 2022: 16 · 2021: 18 · 2020: 16 · 2019: 14 · 2018: 5 · 2017: 5 · 2016: 4
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Funders
- European Molecular Biology Laboratory
- Fonds Wetenschappelijk Onderzoek
- Universiteit Gent
- Vlaamse regering
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- in vitro transcribed mRNA, innate immunity, immune evasion, non-viral gene therapy, mRNA expression
- MeSH terms
- Animals, Humans, Immunity, Innate, Immunotherapy, RNA, Messenger, Genetic Therapy
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