AMG1541 is a biodegradable ionizable lipid engineered by MIT for high-efficiency mRNA delivery. Its design integrates a pH-responsive bicyclic amine headgroup with twin ester-functionalized lipid tails, enabling potent endosomal escape while ensuring rapid metabolic clearance. The fused ring system in the headgroup features a critical β-amino alcohol motif that optimizes acid dissociation behavior, achieving a pKa near physiological thresholds to enhance membrane fusion in acidic compartments. This structural attribute facilitates efficient cytosolic mRNA release.
The lipid tails incorporate hydrolyzable ester bonds derived from long-chain fatty acids, which allow enzymatic degradation in vivo to minimize off-target accumulation and toxicity. AMG1541 demonstrates superior performance in both intramuscular and intravenous delivery, significantly outperforming industry benchmarks like SM-102 and cKK-E12. It drives robust protein expression in muscle tissue, sustains high-level gene editing in the liver, and elicits strong immune responses for vaccine applications.
The stereochemistry of its bicyclic core is essential for activity, with the S-configured isomer showing markedly higher efficacy than its R-counterpart. This molecular architecture exemplifies MIT’s approach to balancing transfection potency with biodegradability, positioning AMG1541 as a versatile platform for therapeutic nucleic acid delivery.
Cat.No
DC67558
Name
AMG1541
Chemical Properties
CAS
Formula
C102H186O18N6
MW
1783.38
Storage
2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
References
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