LNP Reagents for mRNA Delivery in COVID-19 Vaccine Manufacture

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. Products for LNPsAfter being absorbed by the cell, the mRNA delivered by LNPs are released to the cytoplasm and express the target protein, escaping from the endocytosis.

JenKem Technology provides large scale GMP manufacture of PEG derivatives, small molecules, and related PEG intermediates, useful for lipid nanoparticles for COVID-19 vaccine.

Example PEGs for LNPs:

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

Example Small Molecule Reagents for LNPs:

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

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.

PEGs for RNA DeliveryExample Cell Penetrating Peptide PEGs:

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

Please contact us for a quotation.

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. Schoenmaker, Linde, et al., mRNA-lipid nanoparticle COVID-19 vaccines : structure and stability, International Journal of Pharmaceutics 601 (2021).
  2. Ye, J., et al., High-Yield Synthesis of Monomeric LMWP(CPP)-siRNA Covalent Conjugate for Effective Cytosolic Delivery of siRNA, Theranostics (2017).