Determinants of intracellular RNA pharmacokinetics: Implications for RNA-based immunotherapeutics
Open accessAbstract
RNAs with optimized properties are increasingly investigated as a tool to deliver the genetic information of complete antigens into professional antigen-presenting dendritic cells for HLA haplotype-independent antigen-specific vaccination against cancer. As the dose of the antigen and duration of its presentation are critical factors for generating strong and sustained antigen-specific immune responses, improvement of the immunobioavailability of RNA-based vaccines has been a recurrent subject of research. Substantial increase of the amount of antigen produced from RNA can be achieved by optimizing RNA stability and translational efficiency. Both features are determined by cis-acting elements in the RNA, namely the 5' cap, the poly(A) tail, and the sequence of the coding and non-coding regions, which interact with corresponding trans-acting factors. This article summarizes recent developments in identifying optimized RNA for expression of foreign proteins in dendritic cells, as well as their implications for immunotherapy based on antigen-encoding RNA.
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COVID-19 vaccines required intramuscular administration of mRNA-LNP and expression of the mRNA-encoded antigen in antigen-presenting cells such as dendritic cells to induce a protective immune response.
“COVID-19 vaccines required intramuscular administration of mRNA-LNP and expression of the mRNA-encoded antigen in antigen-presenting cells such as dendritic cells (DC) to induce a protective immune response.34”
From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [34]
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- Authors
- Kuhn, A. N., Diken, M., Kreiter, S., Vallazza, B., Türeci, Ö., & Sahin, U.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Venue
- RNA Biology
- Publisher
- Informa UK Limited
- Published
- 2011-01
- Volume
- 8
- Issue
- 1
- Pages
- 35-43
- ISSN
- 1547-6286 (ISSN-L)
- 1555-8584
- OpenAlex
- W2055918824
- Cited by
- 39
- References
- 7
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2018: 4 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 7 · 2012: 2
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 432)
- Bundesministerium für Bildung und Forschung
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- RNA vaccines, dendritic cells, antigen-presenting cells, cancer immunotherapy, RNA stability, translation efficiency, 5' cap, poly(A) tail, cis-regulatory elements, trans-acting factors, antigen-specific immune response
- MeSH terms
- Dendritic Cells, Humans, Immunotherapy, Neoplasms, Poly A, RNA, RNA Caps, Deoxyribonucleases, Type II Site-Specific, Antigen Presentation, Cancer Vaccines, 3' Untranslated Regions, RNA Stability, Polyadenylation, Poly(A)-Binding Proteins
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