JenKem Technology presents several innovative LNP solutions for selective delivery of mRNA and siRNA. Please contact us for information about these products.

JenKem Technology provides large scale GMP manufacture of PEG-lipids, lipids, PEG intermediates for lipid nanoparticles, along with LNP-related services listed below.

  • Innovative lipid products (JK-0315, JK-102, JK-0039, JK-0055, JK-0056) and LNP formulation development, such as Innovative 3-component LNPs and 5-component LNPs for selective organ targeting – see below
  • Large scale GMP manufacture of conventional lipid products (cationic lipids, ionizable lipids, PEG lipids, phospholipids, helper lipids, SORT lipids, and others made-to-order)
  • Development services for Lipid products (lipid process development, quality research, CDE/DMF application)
  • LNP encapsulation services for RNA
  • Analytical testing services (for LNP, RNA, LNP-RNA)

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

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.

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

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

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