306Oi10 is a branched-chain ionizable lipidoid and may be useful in the generation of lipid nanoparticles (LNPs). 306Oi10 ionizable lipids tail is isodecyl acrylate, affording the
lipid tail a carbon branch, which confers significant improvement of the mRNA deliver efficiency. Compared with the straight-tailed 306O10, the 306Oi10 with carbon branches at the lipid tail generates more powerful surface ionization at late endosomal pH of 5.0 to improve the delivery efficiency of mRNA. The studies showed that 306Oi10 iLNPs significantly promoted mRNA expression in liver (more than 10- fold).306Oi10 iLNPs could induce stronger protein expression
than two benchmark lipids, C12-200 and DLin-MC3-DMA. The
total organ protein expression produced by 306Oi10 iLNPs was
threefold higher than MC3 and over 20-fold higher expression
than C12-200. The 306Oi10 iLNPs could codeliver three distinct
mRNAs (luciferase, mCherry, and erythropoietin), or deliver
Cas9 mRNA and single guide RNA (sgRNA) separately.
Besides, 306Oi10 iLNPs have the potential of mRNA therapy
for hepatocellular carcinoma, because they could target
malignant hepatocytes, endothelial cells, and Kupffer cells
simultaneously. To enable 306Oi10 iLNPs to deliver mRNA to
extrahepatic organs, charged phospholipids were used in place
of neutral phospholipids. The substitution of DOPE with
DOTAP increased the positive surface charge of iLNPs at pH
7 about fivefold and changed the protein expression ratio of
liver/lung from 36:1 to 1:56. Similarly, the substitution of
DOPE with PS decreased the positive charge and changed the
protein expression ratio of liver/spleen from 8:1 to 1:3.
Further, the lung-target of DOTAP was better than that of neutral
or anionic lipids, which might reduce immune cells infiltration
in the lung.
Cat.No
DC80066
Name
306Oi10
Chemical Properties
CAS
2322290-93-5
Formula
C59H115N3O8
MW
993.8684
Storage
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
References
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