AUTOMATED CHROMATOGRAPHY AND LNP ASSEMBLY SYSTEM BY INSCINSTECH

Automated chromatography and LNP assembly system accelerate mRNA Vaccines & Therapeutics development

mRNA technology platforms has breakout in pharmaceutical market during the Covid-19 pandemic.It’s potential as alternative to conventional vaccine and also therapeutic drug has attracted dozens of biotech and biopharma companies.Chromatography and LNP assembly are two key technology in mRNA process.There’s strong demands for chromatography system and LNP assembly system. Inscinstech with it’s more than ten year experience in automated equipment development has developed proprietary AutoPure series chromatography and AutoMCD series nanoparticle assembly system to assist mRNA developers for fast process development and lower cost.

LNP delivery system and production

General mRNA vaccine&Therapeutics process include three session- plasmid with target gene production, in vitro transcription of mRNA and purification, LNP assembly & formulation.
How to specifically deliver mRNA into target cells needs to solve three difficulties: extracellular barrier, endosomal escape and intracellular immunity. LNP delivery system has been used as an solution in effectively transporting mRNA to cells and protecting mRNA from degradation.

Lipid Nanoparticle (LNP) is a kind of Nanoparticle formed from lipids. The structure of LNP is a vesicle composed of phospholipid bilayer. By loading the nucleic acid drug into LNP, it protects the coated nucleic acid drug from degradation and clearance, and facilitates its transmembrane transport to the target site. The widely used composition of LNP includes cationic lipid, neutral helper lipid, cholesterol, PEG-lipid and nucleic acid.

In the preparation of LNP, it mainly depends on self-assembly ability, that is, lipid components spontaneously organize into nano structured entities through molecular interaction. First, the negatively charged nucleic acid and positively charged lipids are bonded by static electricity, and then assembled by hydrophobic and van der Waals interactions between lipid components to form LNP.

The traditional preparation method of LNP is simply two-phase mixture and then the particle size is controlled by homogenizing technology (high pressure homogenizer, high pressure micro-jet) or extrusion technology (polycarbonate membrane filter). The nano particles formed a multi-layer structure in which the mRNA molecules were sandwiched in concentric lipid bilayer. The encapsulation rate of this method is generally not high, and it requires high precision and high specialization equipment, which leads to the difficulty of process amplification.

Another technology is ethanol dilution. Various lipids were dissolved in ethanol, mRNA was dissolved in buffer, and the two phases were quickly mixed. By diluting the ethanol phase, the solubility of lipids decreased, and gradually precipitated and solidified in the mixed solution to form lipid nanoparticles. Meanwhile, the mRNA was efficiently encapsulated.

The commercial production of mRNA/LNP uses microfluidic or T-junction mixing technology, which is fast and simple, easy to scale-up and better control of LNP quality (encapsulation rate, particle size and PDI).

The AutoMCD nanoparticle assembly system developed by Inscinstech is an automated system for LNP process development and production. It's widely used in mRNA and oligonucleotide drug nanoparticle production. The accurate and stable flowrate and pressure control, talor-made microfluidic mixing technology makes it an excellent system to achieve good particle size, PDI and encapsulation efficiency.

Chromatography system

Chromatography technology is widely used in plasmid and mRNA purification, and also other nucleic acid, protein, virus downstream process. Unique AutoPure purification system is a fully automated purification system developed and produced by Incinstech. The portfolio includes small scale system of 25ml/min for process development to as large as 600ml/min for scale-up and small scale production compliance with GMP requirement. With automated fraction collecter and intuitive CDSystem software platform, it’s an efficient tool for plasmid and mRNA process development.

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