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Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy
Open accessAbstract
INTRODUCTION: Current gene therapy involves replacement of defective gene by delivery of healthy genetic material to precede normal function. Virus-mediated gene delivery is the most successful and efficient method for gene therapy, but it has been challenged due to serious safety concerns. Conversely, gene delivery using plasmid DNA (pDNA) is considered safer, but its transfection efficiency is much lower than virus-mediated gene transfer. Recently, mRNA has been suggested as an alternative option to avoid undesired insertion of delivered DNA sequences with higher transfection efficiency and stability. AREA COVERED: In this review, we summarize the currently available strategies of mRNA modification to increase the therapeutic efficacy; we also highlight the recent improvements of mRNA delivery for in vivo applications of gene therapy. EXPERT OPINION: The use of mRNA-based gene transfer could indeed be a promising new strategy for gene therapy. Notable advantages include no risk of integration into the genomic DNA, adjustable gene expression and easier modulation of the immune system. By reducing or utilizing the immunogenic properties, mRNA offers a promising tool for gene/or transcript replacement.
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![Figure 1. Typical gene deliveries for therapeutic application. A. pDNA or mRNA-mediated gene transfer is illustrated. pDNA contains the multiple cloning site (MCS), which is used for restriction endonuclease recognition to insert transgene. Mature eukaryotic mRNA consists of five significant portions, including the cap structure ([m7GpppN or m7Gp3N (N: any nucleotide)], the 5’ untranslated region (5’UTR), an open reading frame (ORF), the 3’ untranslated region (3’UTR) and a tail of 100 – 250 adenosine residues (Poly(A) tails). B. Regions of mRNA modifications for increasing their stability. C. Chemical structure of mRNA CAP. D. Standard dinucleotide cap analog. E. Anti-reverse cap analogs (ARCA). F. mRNA degradation pathways. Both major pathways of mRNA decay are initiated by deadenylation.](/paper-figures/885d5bc8f8a9494e95e29a1d408ee6e6/modified-mrna-as-an-alternative-to-plasmid-dna-pdna-for-transcript-replacement-figure-1.jpg)
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“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 [114]
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Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601
Polymeric Delivery of Therapeutic Nucleic Acids
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Boosting intracellular delivery of lipid nanoparticle-encapsulated mRNA
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Metadata
- Authors
- Youn, H., & Chung, J.-K.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Chung, June-Key
- Venue
- Expert Opinion on Biological Therapy
- Publisher
- Informa UK Limited
- Published
- 2015-06-30
- Volume
- 15
- Issue
- 9
- Pages
- 1337-1348
- ISSN
- 1471-2598 (ISSN-L)
- 1744-7682
- PMC
- PMC4696419
- OpenAlex
- W1667670121
- Cited by
- 114
- References
- 73
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 8 · 2023: 17 · 2022: 12 · 2021: 10 · 2020: 8 · 2019: 14 · 2018: 10 · 2017: 7 · 2016: 6
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Expert Opinion on Biological Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Research Foundation (2011-0030001)
- Seoul National University (2011-0030001)
- Ministry of Science, ICT and Future Planning (2011‐0030001)
- Korea Health Industry Development Institute (HI14C1072, HI13C0826)
- National Research Foundation of Korea (2011‐0030001, HI14C1072)
- Seoul National University Hospital
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- mRNA modification, plasmid DNA, gene therapy, therapeutic vaccination, mRNA delivery, transfection efficiency, immunogenicity, in vivo gene therapy
- MeSH terms
- Animals, Humans, Nucleosides, Plasmids, RNA Caps, RNA, Messenger, Transfection, Vaccination, Genetic Therapy, Immunotherapy, Active, Untranslated Regions
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