Leveraging mRNA Sequences and Nanoparticles to Deliver SARS‐CoV‐2 Antigens In Vivo
Open accessAbstract
SARS‐CoV‐2 has become a pandemic worldwide; therefore, an effective vaccine is urgently needed. Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. In this work, the untranslated regions (UTRs) of mRNAs are systematically engineered in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, the optimal combination of 5′ and 3′ UTR are identified and termed NASAR, which are 5‐ to 10‐fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid‐derived TT3 nanoparticles trigger a dramatic expression of potential SARS‐CoV‐2 antigens. The antigen‐specific antibodies induced by TT3‐nanoparticles and NASAR mRNAs are over two orders of magnitude more than that induced by the FDA‐approved lipid nanoparticle material MC3 in vaccinated mice. These NASAR mRNAs merit further development as alternative SARS‐CoV‐2 vaccines.
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UTR performance can vary by cell type, so alternative UTR sequences optimized for the desired application and intended cell target may be used.
“However, because UTR performance can vary by cell type, alternative UTR sequences may be used that have been optimized for the desired application and intended cell target16–18.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [18]
Optimization of the UTRs or the coding sequences results in increased protein expression compared with wild-type controls.
“For example, optimization of the UTRs or the coding sequences results in increased protein expression, compared with wild-type controls107,244.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [107]
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References 49 · Cited by 152
Research works printed but not linked: 1
- [20]Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M, Nature 2011, 473, 337. 21593866
- Authors
- Zeng, C., Hou, X., Yan, J., Zhang, C., Li, W., Zhao, W., Du, S., & Dong, Y.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Dong, Yizhou
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2020-09-02
- Volume
- 32
- Issue
- 40
- Pages
- e2004452-e2004452
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- PMC
- PMC8191860
- OpenAlex
- W3081805696
- Cited by
- 152
- References
- 49
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 22 · 2023: 27 · 2022: 24 · 2021: 33 · 2020: 6
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R35GM119679)
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- COVID-19 vaccines, mRNA vaccines, untranslated regions, lipid nanoparticles, antigen expression, antibody response, mRNA delivery
- MeSH terms
- Betacoronavirus, SARS-CoV-2, COVID-19 Vaccines, Animals, Antibodies, Viral, Antigens, Viral, Female, Humans, Mice, Inbred C57BL, RNA, Messenger, Vaccination, Viral Vaccines, Gene Expression, Coronavirus Infections, Cell Line, Tumor, Nanoparticles, HEK293 Cells
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