Cited by 622RNA Interference and Gene DeliveryImmunotherapy and Immune ResponsesSARS-CoV-2 and COVID-19 Research

Developing mRNA-vaccine technologies

Open access
Schlake, Thomas, Thess, Andreas, Fotin-Mleczek, Mariola, Kallen, Karl-Josef·2012·RNA Biology

Abstract

mRNA vaccines combine desirable immunological properties with an outstanding safety profile and the unmet flexibility of genetic vaccines. Based on in situ protein expression, mRNA vaccines are capable of inducing a balanced immune response comprising both cellular and humoral immunity while not subject to MHC haplotype restriction. In addition, mRNA is an intrinsically safe vector as it is a minimal and only transient carrier of information that does not interact with the genome. Because any protein can be expressed from mRNA without the need to adjust the production process, mRNA vaccines also offer maximum flexibility with respect to development. Taken together, mRNA presents a promising vector that may well become the basis of a game-changing vaccine technology platform. Here, we outline the current knowledge regarding different aspects that should be considered when developing an mRNA-based vaccine technology.

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Crossref · 10.4161/rna.22269

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153 of 153 references verified0 citation errors · 0 not checkable

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  • UTRs can influence mRNA translation efficiency and resistance to degradation by interacting with RNA-binding proteins and microRNAs.

    “It is known that UTRs are associated with processes of mRNA translation, and by interacting with RNA-binding proteins (RBPs) and microRNAs, UTRs can influence mRNA’s translation efficiency and resistance to degradation [3,4,5,6,7].”

    From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [3]

    The mRNA Design section says UTRs affect translation and stability and that miRNA-binding sites in UTRs can destabilize mRNA. The copy does not explain these effects as arising from interactions with RNA-binding proteins; it mentions UTR-binding factors only in a reference title. No page number is available for these passages. (LLM, conf=0.82)

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  • Expression of therapeutic proteins can also be achieved by intramuscular administration (Schlake et al, 2012).

    “Moreover, expression of therapeutic proteins can also be achieved by intramuscular administration (Schlake et al, 2012).”

    From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Schlake et al, 2012

  • The basic structure of mRNA is made up of a protein-encoding ORF, surrounded by 5′ and 3′ UTRs, a 7-methyl guanosine 5′ cap structure, and a 3′ poly(A) tail.

    “The basic structure of mRNA, same as eukaryotic mRNA, is made up of (i) protein encoding ORF, surrounded by (ii) 5′ and 3′ UTRs, and (iii) a 7-methyl guanosine 5′ cap structure and (iv) a 3′poly(A) tail at the end sides (Verbeke et al. 2019; Schlake et al. 2012; Sahin et al. 2014) (Fig. 1).”
  • A non-replicating mRNA contains an open reading frame (ORF) encoding the gene coding for the target antigen flanked by 5′ and 3′ UTR; the 5′ end contains a 7-methylguanosine cap structure, whereas the 3′ end contains a poly(A) tail structure.

    “A non-replicating mRNA contains an open reading frame (ORF) encoding the gene coding for the target antigen flanked by 5′ and 3′ UTR. The 5′ end contains a 7-methylguanosine cap structure (5′-cap, m7G), whereas the 3′ end contains a poly(A) tail structure.”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [113]

  • Poly(A) tails of approximately 100 nt are ideal for synthesizing mRNA therapies because tail size affects mRNA decay by modulating 3′ exonucleolytic degradation.

    “Poly(A) tails of approximately 100 nt are ideal for synthesizing mRNA therapies because tail size affects mRNA decay by modulating 3′ exonucleolytic degradation (Schlake et al. 2012).”

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Authors
Schlake, T., Thess, A., Fotin-Mleczek, M., & Kallen, K.-J.
Affiliations
  • CureVac (Germany) (DE)
  • CureVac GmbH; Tübingen, Germany
Corresponding author
Schlake, Thomas
Venue
RNA Biology
Published
2012-10-12
Volume
9
Issue
11
Pages
1319-1330
ISSN
  • 1547-6286 (ISSN-L)
  • 1555-8584
OpenAlex
W1988620094
Cited by
622
References
153
Citations by year
2026: 34 · 2025: 61 · 2024: 85 · 2023: 117 · 2022: 83 · 2021: 106 · 2020: 38 · 2019: 19 · 2018: 18 · 2017: 22 · 2016: 15 · 2015: 8 · 2014: 10 · 2013: 4 · 2012: 1
FWCI
0.67
Type
journal article
Language
en
Open access
Locations
  • RNA Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
mRNA vaccines, genetic vaccines, humoral and cellular immune response, vaccine safety, vaccine development, vaccine platforms
MeSH terms
Adjuvants, Immunologic, Animals, Biological Transport, Humans, RNA, Messenger, Vaccines, Synthetic, Gene Expression

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