The DOI matches its Crossref record; 38 of the 39 references it cites were found in a registry or an index.
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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“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
Direct Gene Transfer into Mouse Muscle in Vivo
Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., & Felgner, P. L. (1990) · Science · doi:10.1126/science.1690918 · Cited by 4,173
Heterologous Protection Against Influenza by Injection of DNA Encoding a Viral Protein
Ulmer, J. B., Donnelly, J., Parker, S. E., Rhodes, G. H., Felgner, P. L., Dwarki, V., Gromkowski, S. H., Deck, R. R., DeWitt, C. M., Friedman, A., et al. (1993) · Science · doi:10.1126/science.8456302 · Cited by 2,318
mRNA stability in mammalian cells
Ross, J. (1995) · Microbiological Reviews · doi:10.1128/mr.59.3.423-450.1995 · Cited by 1,411
Dannull, J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25947 · Cited by 997
Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.
Boczkowski, D., Nair, S. K., Snyder, D., & Gilboa, E. (1996) · The Journal of experimental medicine · doi:10.1084/jem.184.2.465 · Cited by 915
Cationic liposome-mediated RNA transfection.
Malone, R. W., Felgner, P. L., & Verma, I. M. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.16.6077 · Cited by 911
Regulation of Dendritic Cell Migration to the Draining Lymph Node
Martín-Fontecha, A., Sebastiani, S., Höpken, U. E., Uguccioni, M., Lipp, M., Lanzavecchia, A., & Sallusto, F. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030448 · Cited by 878
How do eucaryotic ribosomes select initiation regions in messenger RNA?
Kozak, M. (1978) · Cell · doi:10.1016/0092-8674(78)90039-9 · Cited by 833
Holtkamp, S., Kreiter, S., Selmi, A., Simon, P., Koslowski, M., Huber, C., Türeci, O., & Sahin, U. (2006) · Blood · doi:10.1182/blood-2006-04-015024 · Cited by 625
Heiser, A., Coleman, D., Dannull, J., Yancey, D., Maurice, M. A., Lallas, C. D., Dahm, P., Niedzwiecki, D., Gilboa, E., & Vieweg, J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214364 · Cited by 562
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Lemonnier, J., & Lemonnier, N. (2023) · Springer eBooks · doi:10.1007/978-3-031-39300-6_12
Additional file 7 of Non-interfacial self-assembly of synthetic protocells
Xu, X., Guan, W., Yu, X., Xu, G., & Wang, C. (2023) · Figshare · doi:10.6084/m9.figshare.23621263
Additional file 2 of Non-interfacial self-assembly of synthetic protocells
Xu, X., Guan, W., Yu, X., Xu, G., & Wang, C. (2023) · Figshare · doi:10.6084/m9.figshare.23621248
Additional file 3 of Non-interfacial self-assembly of synthetic protocells
Xu, X., Guan, W., Yu, X., Xu, G., & Wang, C. (2023) · Figshare · doi:10.6084/m9.figshare.23621251
Additional file 4 of Non-interfacial self-assembly of synthetic protocells
Xu, X., Guan, W., Yu, X., Xu, G., & Wang, C. (2023) · Figshare · doi:10.6084/m9.figshare.23621254
Additional file 6 of Non-interfacial self-assembly of synthetic protocells
Xu, X., Guan, W., Yu, X., Xu, G., & Wang, C. (2023) · Figshare · doi:10.6084/m9.figshare.23621260
Additional file 5 of Non-interfacial self-assembly of synthetic protocells
Xu, X., Guan, W., Yu, X., Xu, G., & Wang, C. (2023) · Figshare · doi:10.6084/m9.figshare.23621257
Additional file 1 of Non-interfacial self-assembly of synthetic protocells
Xu, X., Guan, W., Yu, X., Xu, G., & Wang, C. (2023) · Figshare · doi:10.6084/m9.figshare.23621245
Metadata
- 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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