C14-4 (C14-494,Lipid B-4,Lipid B4) Datasheet DC Chemicals
Description
C14-4 (C14-494,Lipid B-4,Lipid B4) is a novel ionizable lipid with the highest T-cell transfection efficiency and low cytotoxicity.The C14-4 ionizable lipid has been explored for CAR-T therapy.To screen the excellent formulations for mRNA delivery, a
lipid library of 24 ionizable lipids was constructed to make
iLNPs, which were used to deliver luciferase mRNA into
Jurkat cells.[115] The optimal iLNPs formulation was C14-4
iLNPs (C14-4 ionizable lipid, DOPE, chol, and PEG at a molar
ratio of 35%, 16%, 46.5%, and 2.5%) (Figure 6c). The optimal
dose of luciferase mRNA for C14-4 iLNPs was 30 ng.
Compared with electroporated CAR T cells, the CAR T cells engineered
via C14-4 iLNPs showed potent cancer-killing activity
when they were cocultured with Nalm-6 acute lymphoblastic leukemia
cells. To obtain a safer and more effective CAR mRNA
delivery vehicle, the orthogonal design provided 256 potential
formulations, and 16 representative iLNPs formulations were
evaluated.Through evaluating the safety, delivery efficiency,
and transfection efficiency of 16 iLNPs, the formulation B10
(C14-4 ionizable lipid, DOPE, chol, PEG at a molar ratio of
40%, 30%, 25%, and 2.5%) was screened out as the optimal performing formulation. The luciferase expression based on B10
formulation was increased threefold than the initial formulation.
Reducing the accumulation and clearance of iLNPs in the liver
can increase the expression of CAR mRNA in T cells, further
improving the therapeutic effect of CAR-T. Studies have shown
that cholesterol analogs can alter the mechanisms of intracellular
circulation and enhance the delivery of mRNA, which may be
related to the reduced recognition of iLNPs by the Niemann
Pick C1 (NPC1) enzyme.The addition of a hydroxyl
group to various locations in the cholesterol molecule can alter
the binding kinetics between the modified cholesterol and NPC1,
and reduced NPC1 recognition of cholesterol. The results
showed that replacement of 25% and 50% 7 α-hydroxycholesterol
for cholesterol in iLNPs improved mRNA delivery to
primary human T cells in vitro by 1.8-fold and twofold,
respectively.C14-4 is one of the ionizable lipids to efficiently deliver mRNA
to Jurkat cells or primary human T cells. It will effectively promote
the development of mRNA delivery by iLNPs for CAR-T
therapy.
Cat.No
DC59010
Name
C14-4 (C14-494,Lipid B-4,Lipid B4)
Chemical Properties
CAS
2639634-80-1
Formula
C84H173N5O7
MW
1365.30
Storage
-20
References
Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human
CAR T Cell Engineering
Margaret M. Billingsley, Nathan Singh, Pranali Ravikumar, Rui Zhang, Carl H. June,
and Michael J. Mitchell*
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