Description:
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.
Handling:
Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months.
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance,
we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these will be useable for up to one
month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at
least 1 hour.