A Route to Synthesize Ionizable Lipid ALC-0315, a Key Component of the Lipid Matrix of an mRNA Vaccine
- Authors: Boldyrev I.A.1, Shendrikov V.P.1,2, Vostrova A.G.1, Vodovozova E.L.1
-
Affiliations:
- Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
- Mendeleev University of Chemical Technology of Russia
- Issue: Vol 49, No 2 (2023)
- Pages: 216-220
- Section: ПИСЬМА РЕДАКТОРУ
- URL: https://journals.rcsi.science/0132-3423/article/view/145880
- DOI: https://doi.org/10.31857/S0132342323020069
- EDN: https://elibrary.ru/GHQWWK
- ID: 145880
Cite item
Open Access
Access granted
Subscription Access
Abstract
Ionizable lipid ALC-0315 – ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) – is a part of the lipid matrix of the mRNA vaccine for the prevention of infection with the SARS-CoV-2 virus manufactured by Pfizer/BioNTech. This lipid provides effective assembly of the vaccine particle, protection of mRNA from premature degradation, and after endocytosis, promotes the release of nucleic acid into the cytoplasm for further processing. In this paper, a simplified and economical method for producing ALC-0315 is proposed, which can be used in the production of mRNA vaccines.
Keywords
About the authors
I. A. Boldyrev
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: elvod@lipids.ibch.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10
V. P. Shendrikov
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Mendeleev University of Chemical Technology of Russia
Email: elvod@lipids.ibch.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10; Russia, 125047, Moscow, Miusskaya pl. 9
A. G. Vostrova
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Email: elvod@lipids.ibch.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10
E. L. Vodovozova
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
Author for correspondence.
Email: elvod@lipids.ibch.ru
Russia, 117997, Moscow, ul. Miklukho-Maklaya 16/10
References
- Baden L.R., El Sahly H.M., Essink B., Kotloff K., Frey S., Novak R., Diemert D., Spector S.A., Rouphael N., Creech C.B., McGettigan J., Khetan S., Segall N., Solis J., Brosz A., Fierro C., Schwartz H., Neuzil K., Corey L., Gilbert P., Janes H., Follmann D., Marovich M., M.D., Mascola J., Polakowski L., Ledgerwood J., Graham B.S., Bennett H., Pajon R., Knightly C., Leav B., Deng W., Zhou H., Han S., Ivarsson M., Miller J., Zaks T. // N. Engl. J. Med. 2021. V. 384. P. 403–416. https://doi.org/10.1056/NEJMoa2035389
- Anderson E.J., Rouphael N.G., Widge A.T., Jackson L.A., Roberts P.C., Makhene M., Chappell J.D., Denison M.R., Stevens L.J., Pruijssers A.J., McDermott A.B., Flach B., Lin B.C., Doria-Rose N.A., O’Dell S., Schmidt S.D., Corbett K.S., Swanson P.A., Padilla M., Neuzil K.M., Bennett H., Leav B., Makowski M., Albert J., Cross K., Edara V.V., Floyd K., Suthar M.S., Martinez D.R., Baric R., Buchanan W., Luke C.J., Phadke V.K., Rostad C.A., Ledgerwood J.E., Graham B.S., Beigel J.H. // N. Engl. J. Med. 2020. V. 383. P. 2427–2438. https://doi.org/10.1056/NEJMoa2028436
- Polack F.P., Thomas S.J., Kitchin N., Absalon J., Gurtman A., Lockhart S., Perez J.L., Pérez Marc G., Moreira E.D., Zerbini C., Bailey R., Swanson K.A., Roychoudhury S., Koury K., Li P., Kalina W.V., Cooper D., Frenck R.W., Jr., Hammitt L.L., Türeci Ö., Nell H., Schaefer A., Ünal S., Tresnan D.B., Mather S., Dormitzer P.R., Şahin U., Jansen K.U., Gruber W.C. // N. Engl. J. Med. 2020. V. 383. P. 2603–2615. https://doi.org/10.1056/NEJMoa2034577
- 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
- Hou X., Zaks T., Langer R., Dong Y. // Nat. Rev. Mater. 2021. V. 6. P. 1078–1094. https://doi.org/10.1038/s41578-021-00358-0
- Szoka F.C., Xu Y., Zelphati O. // Adv. Drug Deliv. Rev. 1997. V. 24. P. 291. https://doi.org/10.1016/S0169-409X(96)00470-X
- Benenato K.E., Kumarasinghe E.S., Cornebise M. // Patent Application US 20170210697 A1, 2017.
- Ansell S.M., Du X. // Patent US 10166298 B2, 2019.
- Ansell S.M., Du X. // Int. Application WO 2017075531 A1, 2017.
- Neises B., Steglich W. // Angew. Chem. Int. Ed. 1978. V. 17. P. 522–524. https://doi.org/10.1002/anie.197805221
- Gribble G.W., Abdel-Magid A.F. // Sodium Triacetoxyborohydride / In: Encyclopedia of Reagents for Organic Synthesis. https://onlinelibrary.wiley.com/doi/abs/10.1002/9780-470842898.rs112.pub2
- Yan D., Xueming T. // Patent CN 114249662 A, 2022.
- Ramishetti S., Hazan-Halevy I., Palakuri R., Chatterjee S., Naidu Gonna S., Dammes N., Freilich I., Kolik Shmuel L., Danino D., Peer D. // Adv. Mater. 2020. V. 32. P. e1906128. https://doi.org/10.1002/adma.201906128
