4A3-Cit is an ionizable lipid used for the generation of lipid nanoparticles (LNPs). To investigate the role of unsaturated lipid tails in iLNPs, the
nucleophilic amines were added to ester-based linkers, followed
by Michael’s addition to the thiols to construct a library of 91
amino ionizable lipids. Such ionizable lipids were composed
of an ionizable tertiary amine core, an ester-based degradable
linker, and an alkylthiol tail periphery. Through in vitro
and in vivo screening, the iLNPs with 4A3 core and citronellolbased
(Cit) periphery can significantly increase endosome escape
and delivery efficiency of mRNA, leading to 18-fold increase in
protein expression compared with iLNPs without Cit periphery.
Furthermore, the delivery efficiency of mRNA may be associated
with the location/configuration of the unsaturated bond(s) in
lipids. Although lipids with Cit periphery showed excellent
membrane fusion ability to facilitate endosome escape, the
fusion mechanism needs to be further clarified.
Cat.No
DC65001
Name
4A3-Cit
Chemical Properties
CAS
2768211-13-6
Formula
C83H147N3O16S4
MW
1571.33
Storage
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
References
S. M. Lee, Q. Cheng, X. L. Yu, S. Liu, L. T. Johnson, D. J. Siegwart,
Angew. Chem. Int. Ed. 2021, 60, 5848.
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