LNP Reagents for mRNA Delivery (i.e., COVID-19 vaccines)

JenKem Technology provides large scale GMP manufacture of PEG derivatives, small molecules, and related PEG intermediates for lipid nanoparticles such as those used for COVID-19 vaccines formulations and similar applications. We have filed DMFs with China and US FDA for several of these products and have the capability to file other DMFs at customers’ request.

Lipid Nanoparticles (LNPs) are drug delivery systems commonly employed in the field of nucleic acid drugs. The LNP technology has been adopted in recent years for COVID-19 vaccine manufacture¹. LNPs are generally believed to combine with the cell membrane through non-covalent affinity and absorbed by endocytosis. After being absorbed by the cell, the mRNA delivered by LNPs are released to the cytoplasm and express the target protein, escaping from the endocytosis.

Example PEGs for LNPs offered by JenKem Technology:

M-DMG-2000 (Methoxy PEG Dimyristoyl-rac-glycerol, MW 2000)
M-DTA-2000 ALC-0159 (Methoxy PEG Ditetradecylacetamide, MW 2000)*
M-DTDA-3000 (Methoxy PEG Ditetradecylamino, MW 3000)
M-DTDA-5000 (Methoxy PEG Ditetradecylamino, MW 5000)
M-DTDPA-2000 (Methoxy PEG Ditetradecylpropylamino, MW 2000)
M-EPOX-2000 (Methoxy PEG Epoxide, MW 2000)
M-GLC-2000 (Methoxy PEG Glycerol, MW 2000)
and many other PEG derivatives and intermediates
*Sample for research purposes only, not for sale without IP license                                                                            

Example Small Molecule Reagents for LNPs offered by JenKem Technology:

JK-0315-CA (ALC-0315 analogue)
JK-102-CA (SM-102 analogue)
N, N-bistetradecylamine Ditetradecylamine (CAS no: 17361-44-3)

DSPC ((R)-2,3bis(stearoyloxy)propyl (2-(trimethylammonio)ethyl) phosphate)
ALC-0315  ([(4-hydroxybutyl)azanediyl]bis(hexane-6,1-diyl)bis(2-hexyldecanoate, CAS no: 2036272-55-4)*
SM-102 (Heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxO-6-(undecyloxy) hexyl) amino) octanoate), CAS no: 2089251-47-6)*

*Sample for research purposes only, not for sale without IP license

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

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

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.

PEGs for siRNA Delivery

A novel siRNA delivery system, consisting of CPP (cell penetrating peptide) such as LMWP, linked to a PEG, has been developed by JenKem Technology. siRNAs, while potentially very useful as drugs, are easily degraded by nucleases in vivo, and their relatively high molecular weight, negative charge and hydrophilicity inhibit their ability to permeate through cell membranes. Adding a PEG to CPP improves the siRNA drug’s bioavailability² by preventing the self-assembly and formation of intra-molecular hairpin structures between CPP and siRNA.

Example Cell Penetrating Peptide PEGs from JenKem Technology:

OPSS-PEG-LMWP (OPSS PEG LMWP)
MAL-PEG-LMWP (Maleimide PEG LMWP)

Please contact us for a quotation.

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

 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.

Founded in 2001 by experts in PEG synthesis and PEGylation, JenKem Technology specializes exclusively 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.

References:

1. Zhang, L., et al., Controlled production of liposomes with novel microfluidic membrane emulsification for application of entrapping hydrophilic and lipophilic drugs, Journal of Industrial and Engineering Chemistry, 131, 2024, p.470-480.
2. Schoenmaker, Linde, et al., mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability, International Journal of Pharmaceutics 601 (2021).
3. Ye, J., et al., High-Yield Synthesis of Monomeric LMWP(CPP)-siRNA Covalent Conjugate for Effective Cytosolic Delivery of siRNA, Theranostics (2017).