4A3-SC7​​

SKU: orb3033125

Description

4A3-SC7​​ is a proprietary, ionizable lipid component central to the SORT LNP platform developed for targeted organ delivery. It features a unique ​​branched-tail structure​​ designed to enhance mRNA encapsulation and endosomal escape. In the study, it served as the ​​primary ionizable lipid​​ in both Liver SORT LNPs and updated Lung SORT LNPs. For liver targeting, it was formulated at ​​15.04 mol%​​ alongside helper lipids (DOPE: 23.04%, Cholesterol: 38.72%), PEG-lipid (DMG-PEG2000: 3.2%), and the liver-targeting lipid ​​4A3-Cit (20 mol%)​​. This specific composition (Total lipid:RNA = 20:1 wt/wt) yielded LNPs with ​​~74 nm size​​, ​​low PDI (0.17)​​, and ​​high encapsulation efficiency (87%)​​ for large mRNAs like ABE editors (~5000 nt). Its branched-tail architecture was critical for stabilizing nanoparticles encapsulating large RNAs, overcoming a key limitation of previous formulations. 4A3-SC7-based Liver SORT LNPs enabled ​​>40% base editing in hepatocytes​​ in vivo, achieving durable correction of the disease-causing SERPINA1 mutation in PiZ mice and significantly reducing pathological protein aggregates. In the updated DualSORT system, 4A3-SC7 was also paired with ​​DORI​​ (instead of DOTAP) for improved lung targeting, demonstrating its versatility as a foundational ionizable lipid for multi-organ gene editing therapeutics.

Key Properties

• CAS Number: 1857340-77-2
• MW: 1411.07
• Purity: 0.98
• Formula: C₇₁H₁₃₁N₃O₁₆S₄
• SMILES: O=C(CCN(CCCN(CCCN(CCC(OCCOC(C(CSCCCCCCC)C)=O)=O)CCC(OCCOC(C(CSCCCCCCC)C)=O)=O)C)CCC(OCCOC(C(CSCCCCCCC)C)=O)=O)OCCOC(C(CSCCCCCCC)C)=O

Storage & Handling

• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only