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Self-assembled mRNA vaccines
Open accessAbstract
mRNA vaccines have evolved from being a mere curiosity to emerging as COVID-19 vaccine front-runners. Recent advancements in the field of RNA technology, vaccinology, and nanotechnology have generated interest in delivering safe and effective mRNA therapeutics. In this review, we discuss design and self-assembly of mRNA vaccines. Self-assembly, a spontaneous organization of individual molecules, allows for design of nanoparticles with customizable properties. We highlight the materials commonly utilized to deliver mRNA, their physicochemical characteristics, and other relevant considerations, such as mRNA optimization, routes of administration, cellular fate, and immune activation, that are important for successful mRNA vaccination. We also examine the COVID-19 mRNA vaccines currently in clinical trials. mRNA vaccines are ready for the clinic, showing tremendous promise in the COVID-19 vaccine race, and have pushed the boundaries of gene therapy.
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In the citing paper
“As a result, one copy of saRNA produces multiple copies of RNA transcripts by the above-described mechanism to initiate self-amplification of antigen genes in the cell.35,195,196”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [35]
In the citing paper
“Hence, the delivery vector employed in saRNA vaccines must allow for higher loading capacity and encapsulation efficiency.35”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [35]
In the citing paper
“Tfh cells recognize antigens on the APC surface and help to activate B cells, which in turn produce high-affinity virus-neutralizing antibodies.6,55, 56, 57”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [56]
In the citing paper
“Tfh cells further help activate CD8+ cytotoxic T cells that may specifically recognize and eliminate virus-infected cells (Figure 1).6,55, 56, 57”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [56]
In the citing paper
“These lipids can improve nanoparticle properties, such as particle stability, delivery efficacy, tolerability and biodistribution7,14,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“In addition to cationic or ionizable lipids, lipid nanoparticle–mRNA formulations typically contain other lipid components, such as phospholipids (for example, phosphatidylcholine and phosphatidylethanolamine), cholesterol or polyethylene glycol (PEG)-functionalized lipids (PEG-lipids)7,14,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“This structural feature protects mRNA molecules from nuclease degradation and increases nanoparticle stability in physiological fluids17,46.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“Lipid nanoparticle–mRNA formulations manufactured by rapid mixing exhibit a stable nanostructure17,130,131, in which mRNA molecules can be encapsulated in the interior core through electrostatic interactions with the lipids17,131.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“Incorporating PEG-lipids further decreases recognition by the MPS and clearance by renal filtration17,127.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“This technique allows reproducible and scalable production of lipid nanoparticle–mRNA formulations that show high encapsulation efficiency and homogeneous size distribution17,131.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“mRNA-1273 is stored at −15 °C to −20 °C and is directly injected after thawing17, whereas BNT162b2 is stored at −60 °C to −80 °C and requires thawing and dilution by saline before injection17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“mRNA-1273 is stored at −15 °C to −20 °C and is directly injected after thawing17, whereas BNT162b2 is stored at −60 °C to −80 °C and requires thawing and dilution by saline before injection17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“Of note, the authorized COVID-19 mRNA vaccines are both stored in freezing conditions in the presence of sucrose17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“The IVT mRNA molecules used in the mRNA-1273 and BNT162b2 COVID-19 vaccines were prepared by replacing uridine with m1ψ17,19,21, and their sequences were optimized to encode a stabilized pre-fusion spike protein with two pivotal proline substitutions17,19,21.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“For example, the clinical-grade COVID-19 vaccine, mRNA-1273, was produced within a month after the SARS-CoV-2 genome sequence was available15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“About 2, 5 and 6 months from sequence availability, clinical trial phases I, II and III were initiated, respectively15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“Finally, mRNA-1273 obtained Emergency Use Authorization from the FDA and conditional marketing authorization from the EMA within a year15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“These features make lipid nanoparticle–mRNA formulations a flexible and on-demand vaccine platform to rapidly respond to emerging infectious pathogens4,15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“First, mRNA is a non-infective and non-integrating agent with the ability to encode a broad range of antigens4,15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“Since then, lipid nanoparticle–mRNA formulations have emerged as a potent alternative to conventional vaccine platforms, owing to their unique features4,15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
In the citing paper
“Finally, GMP-grade lipid nanoparticle-mRNA vaccines can be manufactured for specific antigens in a short period of time, compared with other vaccine platforms, such as recombinant proteins and inactivated vaccines2,4,15,17.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [17]
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Metadata
- Authors
- Kim, J., Eygeris, Y., Gupta, M., & Sahay, G.
- Affiliations
- Oregon State University (US)
- Corresponding author
- Sahay, Gaurav
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 170
- Pages
- 83-112
- ISSN
- 0169-409X (ISSN-L)
- PMC
- PMC7837307
- OpenAlex
- W3119364115
- Cited by
- 514
- References
- 318
- Citations by year
- 2026: 49 · 2025: 119 · 2024: 105 · 2023: 90 · 2022: 98 · 2021: 53
- FWCI
- 9.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute
- Cystic Fibrosis Foundation
- National Heart and Lung Institute
- National Heart, Lung, and Blood Institute (1R21EY031066, 5R01HL146736, SAHAY19XX0)
- 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
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- mRNA vaccines, self-assembly, mRNA delivery, lipid nanoparticles, COVID-19 vaccines, route of administration, immune activation, gene therapy, vaccine design
- MeSH terms
- COVID-19 Vaccines, mRNA Vaccines, Animals, Humans, RNA, Messenger, Vaccines, Synthetic, Drug Design, Gene Transfer Techniques, Nanotechnology, Nanoparticles
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