A Route to Synthesize Ionizable Lipid ALC-0315, a Key Component of the Lipid Matrix of an mRNA Vaccine

I. A. Boldyrev; Болдырев И. А.; V. P. Shendrikov; Шендриков В. П.; A. G. Vostrova; Вострова А. Г.; E. L. Vodovozova; Водовозова Е. Л.

doi:10.31857/S0132342323020069

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:
1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
2. Mendeleev University of Chemical Technology of Russia
Issue: Vol 49, No 2 (2023)
Pages: 216-220
Section: ПИСЬМА РЕДАКТОРУ
URL: https://rjmseer.com/0132-3423/article/view/670680
DOI: https://doi.org/10.31857/S0132342323020069
EDN: https://elibrary.ru/GHQWWK
ID: 670680

Cite item

Full Text

Open Access
Restricted Access

Access granted
Restricted Access

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

ionizable lipid, ALC-0315, synthesis, lipid nanoparticles, mRNA

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