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.

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.

Dual SORT LNPs for multi-organ base editing-June 2025 Nature Biotechnology-Minjeong Kim1, Daniel J. Siegwart .etl