Effective delivery with enhanced translational activity synergistically accelerates mRNA-based transfection
Abstract
mRNA instead of DNA provides a new and attractive approach for gene therapy and genetic vaccination. Current technologies for mRNA delivery are based on cationic lipids with DOTAP being the most efficient one. We previously reported on the synthesis of an inorganic-organic hybrid carrier by embedding inorganic nano-particles of carbonate apatite onto liposomal carrier DOTAP and demonstrated its high transfection potency of luciferase mRNA both in mitotic and non-mitotic cells. Here we show that in addition to the carrier design for effective endocytosis and release of mRNA to the cytoplasm, enhancement of mRNA translation efficiency is a prerequisite for maximum protein expression. We used the modified cap analog (ARCA) during in vitro transcription of luciferase DNA for proper cap orientation and demonstrated that transfection with ARCA-mRNA resulted in higher protein expression than the mRNA with usual cap structure for both DOTAP and DOTAP-apatite complex. Secondly, exogenous poly(A) was co-delivered with mRNA by the DOTAP-apatite, resulting in very significant expression compared to mRNA delivery only. Finally, when combined both of the effects of smart carrier and the modifications at mRNA translational level, a notable enhancement (100 times) was achieved as compared to the existing DOTAP-based liposome technology. Our findings, therefore, unveiled a novel approach that an effective delivery system can be developed by the improvement of the gene expression level in comb…
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ARCA-capped mRNA boosts and extends protein expression in cultured cells.
“ARCA-capped mRNA has been shown to boost and extend protein expression in cultured cells (Zohra et al. 2007).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Zohra et al. 2007
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- Authors
- Zohra, F. T., Chowdhury, E. H., Tada, S., Hoshiba, T., & Akaike, T.
- Affiliations
- Tokyo Institute of Technology (JP)
- Corresponding author
- Akaike, T.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 358
- Issue
- 1
- Pages
- 373-378
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2075047419
- Cited by
- 71
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 3 · 2016: 3 · 2015: 7 · 2013: 2 · 2012: 2
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- mRNA delivery, mRNA transfection, DOTAP liposomes, mRNA translation efficiency, luciferase expression, gene therapy, genetic immunization, endocytosis
- MeSH terms
- Quaternary Ammonium Compounds, Apatites, Cytoplasm, Endocytosis, Fatty Acids, Monounsaturated, Luciferases, Poly A, RNA Cap Analogs, RNA, Messenger, Transfection, Protein Biosynthesis, Gene Transfer Techniques, Nanoparticles
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