4A3-SC8 is a novel Ionizable amino lipid for RNA delivery.The CRISPR-Cas9 gene editing system has been a hotspot in the
field of gene therapy, especially the gene correction induced by
homology-directed repair (HDR). However, its application has
various obstacles, such as large molecular weight, poor stability,
off-target risk, and the complexity of codeliver multiple genes.
Farbiak et al. established a novel ionizable lipid library consisting
of four distinct amine cores (3A3, 3A5, 4A1, 4A3) and nine
peripheries with different alkyl chain lengths (SC5-SC14), and screened out a class of iLNPs with ability of encapsulating
Cas9 mRNA, sgRNA and donor DNA simultaneously.
The delivery efficiency (quantified by luciferase mRNA expression)
and iLNPs toxicity were evaluated with three different cell
lines (HEK293T, HeLa, and IGROV-1), indicating the formulation
containing 4A3-SC8 was the best. 4A3-SC8 iLNPs successfully
induced HDR in HEK293 cells by one-pot delivery of Cas9
mRNA, sgRNA, and the correct ssDNA template. Confocal
microscopy imaging showed that a portion of blue fluorescence
in cells was corrected to green fluorescence. Furthermore, the
nucleic acid ratios of Cas9: sgRNA: donor DNA loading in
iLNPs at a ratio of 2:1:3 could maximize the HDR efficiency with
the editing efficiency up to 23%, which breaks through the current
bottleneck of HDR efficiency of only 1–5%. This progress is
undoubtedly an important advance in the gene therapy field to
cure diseases caused by genetic mutations.
Cat.No
DC82001
Name
4A3-SC8
Chemical Properties
CAS
1857340-78-3
Formula
C75H139N3O16S4
MW
1467.2
Storage
-20
References
1 Theranostic dendrimer-based lipid nanoparticles containing PEGylated
BODIPY dyes for tumor imaging and systemic mRNA delivery in vivo-Journal of Controlled Release by Hu Xionga, Shuai Liua, Tuo Weia, Qiang Chenga, Daniel J. Siegwarta|||||
2 Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery--Nature Protocols volume 18, pages265–291 (2023)
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