THOR 76 is an ionizable lipid developed for lung-targeted mRNA delivery, synthesized via a high-throughput Ugi four-component reaction (U4CR). It combines spermine (N3, amine core), oleyl aldehyde (A2), oleic acid (C2), and a morpholine-functionalized isonitrile (D3). Remarkably, its crude reaction mixture outperforms purified forms in efficacy, suggesting synergistic impurities or intermediates enhance function. Formulated into lipid nanoparticles (LNPs) with cholesterol, DOPE, and PEG-lipid, THOR 76 LNPs exhibit exceptional lung tropism with secondary spleen affinity after intravenous administration. They efficiently transfect pulmonary endothelial cells, enabling robust gene expression (e.g., Cre recombinase) and significant CRISPR-Cas9-mediated gene editing (1.22% at 0.1 mg/kg dose) in the lungs. With a particle size <150 nm, positive zeta potential, and >90% mRNA encapsulation, THOR 76 achieves targeted delivery while minimizing off-target effects in the liver. Its design overcomes limitations of cationic helper lipids, offering a potent, tolerable platform for treating pulmonary genetic disorders and cancers.
Cat.No
DC60849
Name
THOR 76 Crude
Chemical Properties
CAS
Formula
C98H186O6N8
MW
1572.62
Storage
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
References
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