Ionizable lipid A6 (di(dec-3-yn-1-yl) 9-((4-(dimethylamino) butanoyl)oxy) heptadecanedioate) was developed by modifying
the backbone structure of Dlin-MC3-DMA through introducing alkynyl and ester groups into the lipid tails. Alkyne lipid A6 demonstrated a significant improvement in transfection efficiency (~8.5, ~2.0, and ~2.5-fold higher than the original MC3, C12-200 and cKK-E12 containing LNPs, respectively).The performance
of the A6 coprepared into iLNPs with other amine-containing
lipid materials (cKKE12) was evaluated, and the molar ratio of
the formulation was changed to 35:16.0:46.5:2.5 (A6/cKKE12:
DOPE: Chol: PEG). The results showed that these formulations
synergistically facilitated more effective mRNA delivery and
improved tolerability following single and repeated dosing. It
was confirmed that albumin-associated macrophage phagocytosis
and endocytosis is an apolipoprotein-independent cellular
internalization pathway of iLNPs in the liver.
According to the fusion kinetics, the lipids with highfrequency
tail protrusion and high lateral diffusion coefficient
can perturb and trigger membrane sprouting, which in turn promotes
membrane fusion. The application of iLNPs with those
lipids (such as A6) may be an effective method to further enhance
the release of mRNA in vivo.
Cat.No
DC80050
Name
LIPID A6
Chemical Properties
CAS
Formula
C43H75NO6
MW
701.56
Storage
-20
References
Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver-Lei Miao, Jiaqi Lin, Yuxuan Huang, Linxian Li, Derfogail Delcassian, Yifan Ge, Yunhua Shi & Daniel G. Anderson
Nature Communications volume 11, Article number: 2424 (2020)
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