Vaccination with Messenger RNA (mRNA)
Abstract
Both DNA and mRNA can be used as vehicles for gene therapy. Because the immune system is naturally activated by foreign nucleic acids thanks to the presence of Toll-like Receptors (TLR) in endosomes (TLR3, 7, and 8 detect exogenous RNA, while TLR9 can detect exogenous DNA), the delivery of foreign nucleic acids usually induces an immune response directed against the encoded protein. Many preclinical and clinical studies were performed using DNA-based experimental vaccines. However, no such products are yet approved for the human population. Meanwhile, the naturally transient and cytosolically active mRNA molecules are seen as a possibly safer and more potent alternative to DNA for gene vaccination. Optimized mRNA (improved for codon usage, stability, antigen-processing characteristics of the encoded protein, etc.) were demonstrated to be potent gene vaccination vehicles when delivered naked, in liposomes, coated on particles or transfected in dendritic cells in vitro. Human clinical trials indicate that the delivery of mRNA naked or transfected in dendritic cells induces the expected antigen-specific immune response. Follow-up efficacy studies are on the way. Meanwhile, mRNA can be produced in large amounts and GMP quality, allowing the further development of mRNA-based therapies. This chapter describes the structure of mRNA, its possible optimizations for immunization purposes, the different methods of delivery used in preclinical studies, and finally the results of clinical trial where mRNA is the active pharmaceutical ingredient of new innovative vaccines.
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Many of the obstacles to mRNA vaccine development have been surmounted, and recently there has been a revival in the use of nonamplifying mRNA vaccines for cancer, allergy, and gene therapy.
“However, many of the obstacles to mRNA vaccine development have been surmounted, and recently there has been a revival in the use of nonamplifying mRNA vaccines for cancer (6), allergy (7), and gene therapy (8).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [6]
Naturally transient and cytosolically active mRNA can now be produced at sufficient quantity and quality for human clinical trials and is seen by many as a safer and more potent alternative to pDNA for vaccination.
“Naturally transient and cytosolically active mRNA can now be produced at sufficient quantity and quality for human clinical trials (6) and is seen by many (9) as a safer and more potent alternative to pDNA for vaccination.”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [6]
Long-term stability of RNA during storage has been demonstrated.
“In addition, long-term stability of RNA during storage has been demonstrated (6,40).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [6]
The recent pioneering work of others on the clinical production of smaller (~2 kb) nonamplifying mRNA has established the feasibility of large-scale production of mRNA using an enzymatic transcription reaction.
“The recent pioneering work of others (6) on the clinical production of smaller (∼2 kb) nonamplifying mRNA has established the feasibility of large-scale production of mRNA using an enzymatic transcription reaction.”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [6]
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- Authors
- Pascolo, S.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Pascolo, Steve
- ORCID
- Pascolo, Steve
- Venue
- Handbook of Experimental Pharmacology
- Publisher
- Springer Berlin Heidelberg
- Published
- 2008
- Issue
- 183
- Pages
- 221-235
- ISSN
- 0171-2004 (ISSN-L)
- OpenAlex
- W81585652
- Cited by
- 126
- References
- 39
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 8 · 2022: 8 · 2021: 17 · 2020: 9 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 12 · 2015: 7 · 2014: 13 · 2013: 5 · 2012: 12
- FWCI
- 4.24
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Handbook of experimental pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- mRNA vaccines, mRNA delivery, Toll-like receptors, dendritic cell transfection, liposomal drug delivery, codon usage, mRNA structure, mRNA therapeutics
- MeSH terms
- Adjuvants, Immunologic, Animals, Clinical Trials as Topic, Dendritic Cells, Humans, Monocytes, RNA, Messenger, Transfection, Vaccines, Synthetic, Drug Delivery Systems
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