A33-D268 is an ionizable lipid derived from a 2-aminoimidazole (AM) core, featuring an asymmetric hydrophobic tail structure designed to optimize mRNA interactions. Selected as the top candidate from a 21-lipid library through molecular dynamics (MD) simulations, it demonstrated superior performance: low root mean square deviation (RMSD) and the smallest radius of gyration (Rg), indicating tight mRNA compaction, alongside moderate electrostatic energy and above-average hydrogen bonding for stable encapsulation. Formulated into LNPs, it achieves efficient muscle-specific transfection post-intramuscular injection, rivaling commercial ALC-0315 LNPs. Crucially, it exhibits 29-fold lower hepatic off-target expression, attributed to its inability to leverage serum protein coronas for liver tropism.
Cat.No
DC60872
Name
Lipid A33-D268
Chemical Properties
CAS
Formula
MW
Storage
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
References
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