RAS BiologyБиоорганическая химия Russian Journal of Bioorganic Chemistry

  • ISSN (Print) 0132-3423
  • ISSN (Online) 1998-2860

Ionizable Cationic Lipid for Intracellular RNA Delivery

PII
S19982860S0132342325050246-1
DOI
10.7868/S1998286025050246
Publication type
Article
Status
Published
Authors
Volume/ Edition
Volume 51 / Issue number 5
Pages
1001-1008
Abstract
Ionizable lipids are a key component of the lipid nanoparticle platform for RNA therapy. They ensure the efficient assembly of a lipid–nucleic acid complex, protect it from premature degradation, and after endocytosis, promote the release of RNA into the cytoplasm for further processing. The paper describes the synthesis of a new ionizable cationic lipid that is a diglyceride derivative of tertiary alkylamine – [5-[1,2-di(decanoyloxy)propane-3-iloxy]pentyl-(4-hydroxybutyl)-amino]pentoxy]-2-decanoyloxypropyl] decanoate (An-1). The synthesis is characterized by the simplicity and cost-effectiveness of reagents. Comparative experiments with the well-known ionizable lipid ALC-0315 have shown that An-1 lipid forms lipid nanoparticles (LNPs) similar in size and incorporation efficiency of the model mRNA. LNPs with mRNA of the green fluorescent protein formulated with An-1 lipid transfected cells in culture more efficiently than LNPs formulated with ALC-0315 lipid. It is assumed that the new ionizable lipid can be used in the production of mRNA vaccines.
Keywords
ионизируемый липид синтез липидные наночастицы мРНК
Date of publication
01.05.2025
Year of publication
2025
Number of purchasers
0
Views
4

References

  1. 1. Cullis P.R., Felgner P.L. // Nat. Rev. Drug Discov. 2024. V. 23. P. 709–722. https://doi.org/10.1038/s41573-024-00977-6
  2. 2. Han X., Mitchell M.J., Nie G. // Matter. 2020. V. 3. P. 1948–1975. https://doi.org/10.1016/j.matt.2020.09.020
  3. 3. Han X., Zhang H., Butowska K., Swingle K.L., Alameh M.-G., Weissman D., Mitchell M.J. // Nat. Commun. 2021. V. 12. P. 7233. https://doi.org/10.1038/s41467-021-27493-0
  4. 4. Semple S.C., Akinc A., Chen J., Sandhu A.P., Mui B.L., Cho C.K., Sah D.W., Stebbing D., Crosley E.J., Yaworski E., Hafez I.M., Dorkin J.R., Qin J., Lam K., Rajeev K.G., Wong K.F., Jeffs L.B., Nechev L., Eisenhardt M.L., Jayaraman M., Kazem M., Maier M.A., Srinivasulu M., Weinstein M.J., Chen Q., Alvarez R., Barros S.A., De S., Klimuk S.K., Borland T., Kosovrasti V., Cantley W.L., Tam Y.K., Manoharan M., Ciufolini M.A., Tracy M.A., de Fougerolles A., Mac-Lachlan I., Cullis P.R., Madden T.D., Hope M.J. // Nat. Biotechnol. 2010. V. 28. P. 172–176. https://doi.org/10.1038/nbt.1602
  5. 5. Mrksich K., Padilla M.S., Mitchell M.J. // Adv. Drug Deliv. Rev. 2024. V. 214. P. 115446. https://doi.org/10.1016/j.addr.2024.115446
  6. 6. European Medicines Agency, Comirnaty Assessment Report. COVID-19 mRNA vaccine (nucleoside-modified). https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf
  7. 7. Jörgensen A.M., Wibel R., Bernkop-Schnürch A. // Small. 2023. V. 19. P. 2206968. https://doi.org/10.1002/smll.202206968
  8. 8. Болдырев И.А., Шендриков В.П., Кислова С.О., Потешнова М.В., Андреев Д.Е., Рубцов Ю.П., Рубцова М.П., Водовозова Е.Л. // Патент RU2823298C1, 2024.
  9. 9. Schoenmaker L., Witzigmann D., Kulkarni J.A., Verbeke R., Kersten G., Jiskoot W., Crommelin D.J.A. // Int. J. Pharm. 2021. V. 601. P. 120586. https://doi.org/10.1016/j.ijpharm.2021.120586
  10. 10. Cheng X., Lee R.J. // Adv. Drug Deliv. Rev. 2016. V. 99. P. 129–137. https://doi.org/10.1016/j.addr.2016.01.022
  11. 11. Münter R., Larsen J.B., Andresen T.L. // J. Colloid Interface Sci. 2024. V. 674. P. 139–144. https://doi.org/10.1016/j.jcis.2024.06.158
  12. 12. Schultz D., Münter R.D., Cantín A.M., Kempen P.J., Jahnke N., Andresen T.L., Simonsen J.B., Urquhart A.J. // Eur. J. Pharm. Biopharm. 2024. V. 205. P. 114571. https://doi.org/10.1016/j.ejpb.2024.114571
  13. 13. Zalba S., Ten Hagen T.L.M., Burgui C., Garrido M.J. // J. Control. Release. 2022. V. 351. P. 22–36. https://doi.org/10.1016/j.jconrel.2022.09.002
  14. 14. Fedorovskiy A.G., Antropov D.N., Dome A.S., Puchkov P.A., Makarova D.M., Konopleva M.V., Matveeva A.M., Panova E.A., Shmendel E.V., Maslov M.A., Dmitriev S.E., Stepanov G.A., Markov O.V. // Pharmaceutics. 2024. V. 16. P. 684. https://doi.org/10.3390/pharmaceutics16050684
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