JenKem Technology Inc. and Cansino (Shanghai) Biological Research Co. Ltd. presented a collaborative research poster titled “Novel Ionizable Cationic Lipids and the Corresponding LNPs for Selective Delivery of Nucleic Acids ” at The LNP Formulation & Process Development Summit on April 14-16, 2025 at The Westin Copley Place.
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Lipid nanoparticles (LNPs) typically consist of four components—ionizable lipids, phospholipids, cholesterol, and PEGylated lipids. However, traditional LNPs accumulate in liver after intravenous injection or intramuscular administration, greatly limiting their therapeutic applications. The risk of RNA delivery to off-target tissues highlights the necessity for LNPs with enhanced tissue selectivity. Research has shown that the addition of different types of selective organ targeting (SORT) lipids to traditional LNPs can alter their in vivo delivery profile, achieving targeted delivery of mRNA to various non-liver tissues.
The researchers have developed two types of permanently cationic lipids (JK-0055 & JK-0056), which can form stable SORT LNPs with traditional LNPs. In vitro experiments have shown that two types of SORT LNPs carrying GFP mRNA can stably express green fluorescent protein after being transfected into Hep3b cells. In vivo experiments have shown that two types of SORT LNPs can specifically concentrate in the lungs of mice after intravenous injection.
The researchers also designed a novel ionizable steryl lipids (ISLs) based three components LNP (3C-LNP)，which exhibited high efficiency of mRNA encapsulation and excellent stability during storage. In vitro assays indicated that C3-JK-0039 LNPs achieved targeted delivery specifically to keratinocytes, without affecting breast cancer cells. Additionally, the C3-LNPs demonstrated no cytotoxicity in CCK-8 assays and did not induce skin allergies in vivo. What is more, the 3C-LNPs were identified as local mRNA delivery systems through intramuscular administration.
Both JK-0055 and JK-0056 based SORT LNPs can be taken up by cells in vitro and specifically accumulated to lungs in vivo. C3-JK-0039 LNPs is a potential muscle-targeted delivery system with high efficiency of mRNA encapsulation, excellent stability and a good safety profile.
