Open Access
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volume 16 issue 5 pages 684

Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues

Artem G. Fedorovskiy 1, 2
Denis N Antropov 3
Anton Dome 3
Pavel A. Puchkov 2
Daria M. Makarova 2
Maria V Konopleva 1, 2, 4
Anastasiya M Matveeva 3
Eugenia A. Panova 1
Sergey E. Dmitriev 1, 4, 5
Publication typeJournal Article
Publication date2024-05-19
scimago Q1
wos Q1
SJR1.075
CiteScore10.0
Impact factor5.5
ISSN19994923
Abstract

Over the past decade, mRNA-based therapy has displayed significant promise in a wide range of clinical applications. The most striking example of the leap in the development of mRNA technologies was the mass vaccination against COVID-19 during the pandemic. The emergence of large-scale technology and positive experience of mRNA immunization sparked the development of antiviral and anti-cancer mRNA vaccines as well as therapeutic mRNA agents for genetic and other diseases. To facilitate mRNA delivery, lipid nanoparticles (LNPs) have been successfully employed. However, the diverse use of mRNA therapeutic approaches requires the development of adaptable LNP delivery systems that can control the kinetics of mRNA uptake and expression in target cells. Here, we report effective mRNA delivery into cultured mammalian cells (HEK293T, HeLa, DC2.4) and living mouse muscle tissues by liposomes containing either 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) or the newly applied 1,30-bis(cholest-5-en-3β-yloxycarbonylamino)-9,13,18,22-tetraaza-3,6,25,28-tetraoxatriacontane tetrahydrochloride (2X7) cationic lipids. Using end-point and real-time monitoring of Fluc mRNA expression, we showed that these LNPs exhibited an unusually delayed (of over 10 h in the case of the 2X7-based system) but had highly efficient and prolonged reporter activity in cells. Accordingly, both LNP formulations decorated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) provided efficient luciferase production in mice, peaking on day 3 after intramuscular injection. Notably, the bioluminescence was observed only at the site of injection in caudal thigh muscles, thereby demonstrating local expression of the model gene of interest. The developed mRNA delivery systems hold promise for prophylactic applications, where sustained synthesis of defensive proteins is required, and open doors to new possibilities in mRNA-based therapies.

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Fedorovskiy A. G. et al. Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues // Pharmaceutics. 2024. Vol. 16. No. 5. p. 684.
GOST all authors (up to 50) Copy
Fedorovskiy A. G., Antropov D. N., Dome A., Puchkov P. A., Makarova D. M., Konopleva M. V., Matveeva A. M., Panova E. A., Shmendel E., Maslov M., Dmitriev S. E., Stepanov G. A., Markov O. V. Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues // Pharmaceutics. 2024. Vol. 16. No. 5. p. 684.
RIS |
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RIS Copy
TY - JOUR
DO - 10.3390/pharmaceutics16050684
UR - https://www.mdpi.com/1999-4923/16/5/684
TI - Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues
T2 - Pharmaceutics
AU - Fedorovskiy, Artem G.
AU - Antropov, Denis N
AU - Dome, Anton
AU - Puchkov, Pavel A.
AU - Makarova, Daria M.
AU - Konopleva, Maria V
AU - Matveeva, Anastasiya M
AU - Panova, Eugenia A.
AU - Shmendel, Elena
AU - Maslov, Michael
AU - Dmitriev, Sergey E.
AU - Stepanov, Grigory A
AU - Markov, Oleg V
PY - 2024
DA - 2024/05/19
PB - MDPI
SP - 684
IS - 5
VL - 16
PMID - 38794346
SN - 1999-4923
ER -
BibTex |
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BibTex (up to 50 authors) Copy
@article{2024_Fedorovskiy,
author = {Artem G. Fedorovskiy and Denis N Antropov and Anton Dome and Pavel A. Puchkov and Daria M. Makarova and Maria V Konopleva and Anastasiya M Matveeva and Eugenia A. Panova and Elena Shmendel and Michael Maslov and Sergey E. Dmitriev and Grigory A Stepanov and Oleg V Markov},
title = {Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues},
journal = {Pharmaceutics},
year = {2024},
volume = {16},
publisher = {MDPI},
month = {may},
url = {https://www.mdpi.com/1999-4923/16/5/684},
number = {5},
pages = {684},
doi = {10.3390/pharmaceutics16050684}
}
MLA
Cite this
MLA Copy
Fedorovskiy, Artem G., et al. “Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues.” Pharmaceutics, vol. 16, no. 5, May. 2024, p. 684. https://www.mdpi.com/1999-4923/16/5/684.