mRNA vaccine delivery using lipid nanoparticles

Reichmuth, Andreas M; Oberli, Matthias A; Jaklenec, Ana; Langer, Robert; Blankschtein, Daniel

doi:10.4155/tde-2016-0006

Cited by 624RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvancements in Transdermal Drug Delivery

mRNA vaccine delivery using lipid nanoparticles

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Reichmuth, Andreas M, Oberli, Matthias A, Jaklenec, Ana, Langer, Robert, Blankschtein, Daniel·2016·Therapeutic Delivery

DOI 10.4155/tde-2016-0006PMC PMC5439223

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Abstract

mRNA vaccines elicit a potent immune response including antibodies and cytotoxic T cells. mRNA vaccines are currently evaluated in clinical trials for cancer immunotherapy applications, but also have great potential as prophylactic vaccines. Efficient delivery of mRNA vaccines will be key for their success and translation to the clinic. Among potential nonviral vectors, lipid nanoparticles are particularly promising. Indeed, lipid nanoparticles can be synthesized with relative ease in a scalable manner, protect the mRNA against degradation, facilitate endosomal escape, can be targeted to the desired cell type by surface decoration with ligands, and as needed, can be codelivered with adjuvants.

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Modifications to the spike protein are intended to reduce the innate immune response by inhibiting proinflammatory cytokines, while the lipid nanoparticle vehicle/EV for the mRNA acts as an adjuvant to enhance the immune response.
“Modifications to the spike protein are intended to reduce the innate immune response by inhibiting proinflammatory cytokines, while at the same time, the lipid nanoparticle vehicle/EV for the mRNA acts as an adjuvant to enhance the immune response. 194-196”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [196]
In “Adjuvanting lipid nanoparticles,” the paper says the LNP vector can itself have an adjuvant effect and that some lipids activate the immune system. It does not support the claim about modifying the spike protein to inhibit proinflammatory cytokines; its discussion of suppressing innate immune activation concerns modified mRNA nucleotides, not spike protein. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Intracellular delivery of oligonucleotides can be improved by encapsulating them in lipid nanoparticles (LNP).
“Intracellular delivery of oligonucleotides can be improved by encapsulating them in lipid nanoparticles (LNP) [9], [23]”
From Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial (2021) · cites this paper as [23]
The ionizable cationic lipid contains positively charged ionizable amine groups (at low pH) to interact with the anionic mRNA during particle formation and facilitate membrane fusion during internalization.
“The latter contains positively charged ionizable amine groups (at low pH) to interact with the anionic mRNA during particle formation and also facilitate membrane fusion during internalization (Evers et al., 2018, Reichmuth et al., 2016).”
From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Reichmuth et al., 2016
With the advancement of lipid nanoparticle techniques, mRNA vaccine stability can be maintained under less rigorous settings.
“However, with the advancement of lipid nanoparticle techniques, mRNA vaccine stability can be maintained under less rigorous settings (Reichmuth et al. 2016).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Reichmuth et al. 2016

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Background
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BackgroundInfluential
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Authors: Reichmuth, A. M., Oberli, M. A., Jaklenec, A., Langer, R., & Blankschtein, D.
Affiliations: Koch Institute for Integrative Cancer Research At MIT (US)
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA
Massachusetts Institute of Technology (US)
ORCID: Reichmuth, Andreas M
Oberli, Matthias A
Jaklenec, Ana
Blankschtein, Daniel
Venue: Therapeutic Delivery
Publisher: Informa UK Limited
Published: 2016-04-14
Volume: 7
Issue: 5
Pages: 319-334
ISSN: 2041-5990 (ISSN-L)
2041-6008
DOI: 10.4155/tde-2016-0006
PMC: PMC5439223
OpenAlex: W2340049980
Cited by: 624
References: 146
Citations by year: 2026: 41 · 2025: 76 · 2024: 89 · 2023: 89 · 2022: 118 · 2021: 128 · 2020: 44 · 2019: 13 · 2018: 20 · 2017: 3 · 2016: 3
FWCI: 1.17
Type: journal article
Language: en
Update notices: correction (2016-06-10)
Open access: green
europepmc.org
Locations: Therapeutic Delivery (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
Funders: National Institutes of Health (4r37eb000244-34)
National Institute of Biomedical Imaging and Bioengineering (EB-000244, R01EB000244, R37-EB000244)
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 › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
Keywords: mRNA vaccines, lipid nanoparticles, mRNA delivery, non-viral vectors, endosomal escape, adjuvants, cancer immunotherapy, prophylactic vaccines, mRNA stability
MeSH terms: Animals, Lipids, Macaca, Rabbits, RNA, Messenger, Vaccines, Drug Delivery Systems, Mice, Nanoparticles

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