Ionizable Cationic Lipid for Intracellular RNA Delivery

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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.

作者简介

K. Gaisin

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Lomonosov Moscow State University, Faculty of Chemistry

Moscow, Russia; Moscow, Russia

E. Ryabukhina

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Moscow, Russia

D. Koroev

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Moscow, Russia

I. Mikhalyov

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Moscow, Russia

E. Zhuravlev

Institute of Chemical Biology and Fundamental Medicine SB RAS

Novosibirsk, Russia

G. Stepanov

Institute of Chemical Biology and Fundamental Medicine SB RAS

Novosibirsk, Russia

I. Boldyrev

Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences

Moscow, Russia

E. Vodovozova

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: elvod.ibch@yandex.ru
Moscow, Russia

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