JenKem Technology provides large scale GMP manufacture of PEG-lipids, lipids, PEG intermediates for lipid nanoparticles, along with LNP formulation services and innovative LNP solutions for selective delivery of mRNA, siRNA for RNA therapeutics. Herein we present several examples of innovative lipid nanoparticle formulation projects completed by JenKem Technology.

Novel Ionizable Lipid JK-102 Enables Efficient mRNA Delivery and Robust T-Cell Responses Comparable to SM-102

Iterative Design of Novel Ionizable Steryl Lipid (ISL) Based 3-Component Lipid Nanoparticles (3C-LNPs) for Intramuscular Delivery of mRNA Vaccines

RNA-based therapies including mRNA, siRNA, and ASO, have shown great promise in treating a broad spectrum of diseases such as infections, tumors, and rare diseases. Most recently, two vaccines of lipid nanoparticles (LNPs) encapsulating mRNA, mRNA1273 and BNT162b2, have achieved great success in the prevention and control of COVID-19 pandemic. Conventional LNPs are formulated with four lipid components including ionizable lipid, cholesterol, PEG-lipid, and helper lipid. The functional delivery of mRNA by LNP greatly depends on the inclusion of ionizable lipids. The risk of mRNA delivery to off-target tissues highlights the necessity for LNPs with enhanced tissue selectivity. mRNA delivered by conventional LNPs after intramuscular administration partly reaches the liver and results in substantial expression of the target proteins in the liver. Herein, we showed that the iterative design of novel ionizable steryl lipids (ISLs) based on three-components LNP (3C-LNP) exhibited high efficiency of mRNA encapsulation and delivery, good safety profile, and excellent stability during storage. Furthermore, the 3C-LNPs were identified as local mRNA delivery systems through intramuscular administration. It manifested high transfection efficiencies at local sites without systemic exposure which minimized systemic side effects. This collaborative study with CanSino Biologics Inc. (CanSinoBIO) indicated that the ISL-3C-LNPs have great potential for mRNA vaccine delivery, which is prioritized for the CD8+T cell activation such as mRNA tumor vaccine. Meanwhile, the local delivery feature of the ISL-3C-LNPs introduces a promising approach for safe and effective gene therapy targeting muscle tissue.

Novel Ionizable Cationic Lipids and the Corresponding LNPs for Selective Delivery of Nucleic Acids

JenKem Technology has 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. We 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.
In conclusion, 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.

Design of Novel Permanently Cationic Lipids (PCL) Based SORT Lipid Nanoparticles (SORT LNPs) for Specific Delivery of mRNA to Lungs in Mice

Lipid nanoparticles (LNPs) typically consist of four components—ionizable lipids, phospholipids, cholesterol, and PEGylated lipids. Approved mRNA COVID-19 vaccines benefit from this delivery system. However, traditional LNPs accumulate in the liver and are internalized by liver hepatocytes after intravenous injection, greatly limiting their therapeutic applications. 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. JenKem Technology has 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. This differs from the in vivo distribution of traditional 4-component LNPs, which only accumulated significantly in the liver of mice after intravenous injection. In summary, this study developed two SORT LNPs that can be taken up by cells in vitro and specifically accumulated to lungs in vivo. These SORT LNPs provide a promising and innovative method for the lung-specific delivery of nucleic acid drugs, with the potential to significantly improve the treatment of lung diseases.

A Novel Ionizable Steryl Lipid (ISL) Based 3-Component Lipid Nanoparticles (3C-LNPs) for Selective Delivery of siRNA

 Currently, six siRNA drugs have been approved to treat from rare to common chronic disease, demonstrating the prospective application of RNAi therapy. siRNA are usually delivered by LNPs or GalNAc conjugates (for intrahepatic applications). However, existing LNP formulation lack the capability for precise siRNA delivery to specific extrahepatic organ. To overcome this limitation, here we have developed a three-components LNP (C3-LNPs) based on a novel ionizable steryl lipid and investigated whether the C3-LNPs could deliver siRNA in a cell-specific manner. 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. These results lay a preliminary foundation for the development of targeted siRNA delivery for specific tissues or organs, though further investigations are necessary to exactly understand their therapeutic potential in vivo.

 Example Cationic Lipids for LNPs:

DOTAP (1,2-dioleoyl-3-trimethylammonium propane, chloride salt)

Example Phospholipids (Helper Lipids) for LNPs:

DSPC ((R)-2,3bis(stearoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate)

Example PEG Lipids for LNPs:

and many other PEG lipid derivatives and intermediates.
*Products marked with * may require a license or authorization in certain jurisdictions. Please contact us for details.

Example Ionizable Lipids for LNPs:

and many other lipids.
*Products marked with * may require a license or authorization in certain jurisdictions. Please contact us for details.

References:

1. Xu, Y., et al., Biomineralized nanoemulsion delivers mRNA for potent cancer immunotherapy, Journal of Controlled Release, 394, 2026.
2. Li, H., et al., Preclinical evaluation of an mRNA vaccine developed from the first human isolate of bovine H5N1, Cell Reports Medicine, 7(4), 2026
3. Wu, W., et al., Preclinical efficacy of engineered CircRNA-GDF15@LNP for sustained weight loss and metabolic regulation in diet-induced obese mice, Journal of Controlled Release, 397, 2026.
4. Wang, Z., et al., Ionizable Sterol Lipid-Based Three-Component Lipid Nanoparticles for Localized Delivery of mRNA Vaccine with Stronger Cellular Immune Responses, ACS Applied Materials & Interfaces, Article ASAP, 2025.
5. Ling, D., et al., A new type of lipid nanoparticles with sphingomyelin-induced active lipid raft structures for improved mRNA cellular uptake, Journal of Controlled Release, 2026, 391.
6. Liu, S., et al, Spleen-targeted mRNA delivery via long-chain PEGylated lipids at low molar ratio enhances antitumor immunity against melanoma, Molecular Therapy Nucleic Acids, 37(1), 2026

Founded in 2001 by experts in PEG synthesis and PEGylation, JenKem Technology specializes in the development and manufacturing of high quality polyethylene glycol (PEG) products and derivatives, and related custom synthesis and PEGylation services. JenKem Technology is ISO 9001 and ISO 13485 certified, and adheres to ICH Q7 guidelines for GMP manufacture. The production of JenKem® PEGs is back-integrated to in-house polymerization from ethylene oxide, enabling facile traceability for regulated customers. JenKem Technology caters to the PEGylation needs of the pharmaceutical, biotechnology, medical device and diagnostics, and emerging chemical specialty markets, from laboratory scale through large commercial scale.