Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics : getting the message across
- Author
- An-Katrien Minnaert (UGent) , Helena Vanluchene (UGent) , Rein Verbeke (UGent) , Ine Lentacker (UGent) , Stefaan De Smedt (UGent) , Koen Raemdonck (UGent) , Niek Sanders (UGent) and Katrien Remaut (UGent)
- Organization
- Project
-
- Genetische therapy voor EYS- en USH2A-geassociëerde retinale dystrofie (‘GET-READY’)
- Barriers and carriers for non-viral delivery of mRNA to induce transient protein expression in the retina: the hurdles of the inner limiting membrane and innate immunity versus the potential of mRNA self-amplification.
- The barrier role of the vitreoretinal interface toward intravitreal injected proteins, viruses and siRNA nanoparticles: ex vivo bovine screening models and siRNA nanoparticle design.
- DeLNAM (Strengthening the Research Area of Delivery of Nucleic acid mimics (NAMS) into bacteria to fight the antibiotic crisis)
- High intensity focused ultrasound and mRNA nanomedicines: a new strategy to induce and boost anti-tumor immunity
- Proteomics-derived epitopes for dramatically improved anticancer and antibacterial vaccine development
- Smart design nanoParticles to Activate immune Responses against Cancer (SPARC)
- Abstract
- The recent approval of messenger RNA (mRNA)-based vaccines to combat the SARS-CoV-2 pandemic highlights the potential of both conventional mRNA and self-amplifying mRNA (saRNA) as a flexible immunotherapy platform to treat infectious diseases. Besides the antigen it encodes, mRNA itself has an immune-stimulating activity that can contribute to vaccine efficacy. This self-adjuvant effect, how-ever, will interfere with mRNA translation and may influence the desired therapeutic outcome. To further exploit its potential as a versatile therapeutic platform, it will be crucial to control mRNA's innate immune-stimulating properties. In this regard, we describe the mechanisms behind the innate immune recognition of mRNA and provide an extensive overview of strategies to control its innate immune-stimulating activity. These strategies range from modifications to the mRNA backbone itself, optimization of production and purification processes to the combination with innate immune inhibitors. Furthermore, we discuss the delicate balance of the self-adjuvant effect in mRNA vaccination strategies, which can be both beneficial and detrimental to the therapeutic outcome.
- Keywords
- mRNA, Self-amplifying mRNA (saRNA), Innate immune stimulation, Type I IFNs, Immune evasion strategies, mRNA vaccination, PERFORMANCE LIQUID-CHROMATOGRAPHY, DEPENDENT PROTEIN-KINASE, NF-KAPPA-B, DENDRITIC CELLS, IN-VITRO, STRANDED-RNA, NUCLEOSIDE MODIFICATIONS, SINDBIS VIRUS, NONCYTOPATHIC REPLICATION, ANTIGEN AVAILABILITY
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8739558
- MLA
- Minnaert, An-Katrien, et al. “Strategies for Controlling the Innate Immune Activity of Conventional and Self-Amplifying MRNA Therapeutics : Getting the Message Across.” ADVANCED DRUG DELIVERY REVIEWS, edited by An-Katrien Minnaert, vol. 176, 2021, doi:10.1016/j.addr.2021.113900.
- APA
- Minnaert, A.-K., Vanluchene, H., Verbeke, R., Lentacker, I., De Smedt, S., Raemdonck, K., … Remaut, K. (2021). Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics : getting the message across. ADVANCED DRUG DELIVERY REVIEWS, 176. https://doi.org/10.1016/j.addr.2021.113900
- Chicago author-date
- Minnaert, An-Katrien, Helena Vanluchene, Rein Verbeke, Ine Lentacker, Stefaan De Smedt, Koen Raemdonck, Niek Sanders, and Katrien Remaut. 2021. “Strategies for Controlling the Innate Immune Activity of Conventional and Self-Amplifying MRNA Therapeutics : Getting the Message Across.” Edited by An-Katrien Minnaert. ADVANCED DRUG DELIVERY REVIEWS 176. https://doi.org/10.1016/j.addr.2021.113900.
- Chicago author-date (all authors)
- Minnaert, An-Katrien, Helena Vanluchene, Rein Verbeke, Ine Lentacker, Stefaan De Smedt, Koen Raemdonck, Niek Sanders, and Katrien Remaut. 2021. “Strategies for Controlling the Innate Immune Activity of Conventional and Self-Amplifying MRNA Therapeutics : Getting the Message Across.” Ed by. An-Katrien Minnaert. ADVANCED DRUG DELIVERY REVIEWS 176. doi:10.1016/j.addr.2021.113900.
- Vancouver
- 1.Minnaert A-K, Vanluchene H, Verbeke R, Lentacker I, De Smedt S, Raemdonck K, et al. Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics : getting the message across. Minnaert A-K, editor. ADVANCED DRUG DELIVERY REVIEWS. 2021;176.
- IEEE
- [1]A.-K. Minnaert et al., “Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics : getting the message across,” ADVANCED DRUG DELIVERY REVIEWS, vol. 176, 2021.
@article{8739558,
abstract = {{The recent approval of messenger RNA (mRNA)-based vaccines to combat the SARS-CoV-2 pandemic highlights the potential of both conventional mRNA and self-amplifying mRNA (saRNA) as a flexible immunotherapy platform to treat infectious diseases. Besides the antigen it encodes, mRNA itself has an immune-stimulating activity that can contribute to vaccine efficacy. This self-adjuvant effect, how-ever, will interfere with mRNA translation and may influence the desired therapeutic outcome. To further exploit its potential as a versatile therapeutic platform, it will be crucial to control mRNA's innate immune-stimulating properties. In this regard, we describe the mechanisms behind the innate immune recognition of mRNA and provide an extensive overview of strategies to control its innate immune-stimulating activity. These strategies range from modifications to the mRNA backbone itself, optimization of production and purification processes to the combination with innate immune inhibitors. Furthermore, we discuss the delicate balance of the self-adjuvant effect in mRNA vaccination strategies, which can be both beneficial and detrimental to the therapeutic outcome.}},
articleno = {{113900}},
author = {{Minnaert, An-Katrien and Vanluchene, Helena and Verbeke, Rein and Lentacker, Ine and De Smedt, Stefaan and Raemdonck, Koen and Sanders, Niek and Remaut, Katrien}},
editor = {{Minnaert, An-Katrien}},
issn = {{0169-409X}},
journal = {{ADVANCED DRUG DELIVERY REVIEWS}},
keywords = {{mRNA,Self-amplifying mRNA (saRNA),Innate immune stimulation,Type I IFNs,Immune evasion strategies,mRNA vaccination,PERFORMANCE LIQUID-CHROMATOGRAPHY,DEPENDENT PROTEIN-KINASE,NF-KAPPA-B,DENDRITIC CELLS,IN-VITRO,STRANDED-RNA,NUCLEOSIDE MODIFICATIONS,SINDBIS VIRUS,NONCYTOPATHIC REPLICATION,ANTIGEN AVAILABILITY}},
language = {{eng}},
pages = {{22}},
title = {{Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics : getting the message across}},
url = {{http://doi.org/10.1016/j.addr.2021.113900}},
volume = {{176}},
year = {{2021}},
}
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