AA2 lipid is an innovative amino alcohol-derived ionizable lipid designed for optimized mRNA delivery. Its unique structure includes a hydroxyl-containing headgroup that enhances mRNA binding through hydrogen bonds and a branched ester tail (R2) that promotes a cone-shaped architecture, facilitating efficient endosomal escape. Formulated into lipid nanoparticles (LNPs) with a size of 108.6 ± 3.7 nm and a polydispersity index (PDI) below 0.3, AA2 achieves high mRNA encapsulation efficiency (89.0 ± 1.4%) and an ideal pKa of approximately 6.2, ensuring effective endosomal release.In vivo studies demonstrate that AA2 LNP-encapsulated spike mRNA elicits 4.7-fold higher IgG titers and robust CD8+ T-cell responses (characterized by IFN-γ+, TNF-α+, and granzyme B+ markers) compared to SM-102/ALC-0315 LNPs. Notably, AA2 exhibits minimal off-target accumulation, with low biodistribution in the liver and spleen. Its slightly positive surface charge (+3–5 mV) enhances cellular uptake, while the biodegradable ester structure ensures metabolic clearance, reducing potential toxicity.
Cat.No
DC67314
Name
Lipid AA2
Chemical Properties
CAS
Formula
MW
Storage
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
References
LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment
Y Xue, X Hou, Y Zhong, Y Zhang, S Du, DD Kang… - Nature Communications, 2025
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