# mRNA and lipid nanoparticle manufacturing

Source: https://onco.cc/technologies/mrna-lnp-manufacturing/  
OnCo record `mrna-lnp-manufacturing` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An mRNA cancer vaccine is made without cells: a DNA template is copied into RNA by an enzyme in a tank, cleaned up, and wrapped in tiny fat bubbles. For personalised vaccines the whole run is done once for each patient, against that patient's own tumour mutations, in a few weeks.

## Summary

mRNA manufacture begins with a plasmid DNA template (covered in the plasmid record), which is linearised and transcribed in vitro by T7 RNA polymerase with a cap analogue and modified nucleotides. The RNA is purified by tangential flow filtration and chromatography (oligo-dT affinity, and reverse-phase or cellulose steps that remove the double-stranded RNA that triggers unwanted inflammation), then mixed with an ionisable lipid, a phospholipid, cholesterol and a PEG-lipid in a microfluidic or T-junction mixer so lipid nanoparticles self-assemble around it. The particles are buffer-exchanged, sterile-filtered, filled and frozen. Every step is cell-free, which is why COVID-19 vaccines could be scaled in months, and the same enzymes, cap analogues, lipids and single-use mixers are the supply chain for cancer vaccines.

Personalised neoantigen vaccines change the logistics. For intismeran autogene (mRNA-4157, Moderna with Merck) the tumour and blood are sequenced, up to thirty-four neoantigens are chosen by algorithm, a patient-specific plasmid is made and the RNA and nanoparticle steps are run as a single-patient GMP batch, with a turnaround of weeks; Moderna produces these at its Norwood, Massachusetts, site and has built a dedicated individualised therapy facility in Marlborough. BioNTech makes autogene cevumeran in Mainz on a similar cycle. Constraints are ionisable lipid patents and supply, enzyme and cap analogue suppliers, and the per-patient release testing that has to be as fast as the manufacture. A Phase 3 trial in melanoma (with pembrolizumab) and trials in lung and pancreatic cancer will decide whether this factory model is worth industrialising.

## Fields

- Kind: Technology
- Status: phase-3
- Last checked: 2026-09-17
- Tags: manufacturing-wave
- Principle: Cell-free enzymatic synthesis of RNA from a DNA template, purified and encapsulated in self-assembling lipid nanoparticles; personalised products run the whole chain once per patient.
- Since: 2020
- Strengths: No cell culture, so weeks not months; Sequence can change without changing the process; Same platform for shared and personalised antigens
- Limitations: Cold chain at minus 20 or minus 70 degrees; Lipid and enzyme supply and patents; Per-patient release testing must keep pace

## Sources

- FDA guidance: CMC information for human gene therapy INDs: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemistry-manufacturing-and-control-cmc-information-human-gene-therapy-investigational-new-drug
- Wikipedia: https://en.wikipedia.org/wiki/MRNA_vaccine

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [Cryopreservation and cell-therapy cold chain](https://onco.cc/technologies/cell-therapy-cold-chain/), [Off-the-shelf cancer vaccines](https://onco.cc/technologies/shared-antigen-vaccine/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/), [Plasmid DNA and mRNA raw-material manufacturing](https://onco.cc/technologies/plasmid-dna-manufacturing/), [Single-use bioprocessing systems](https://onco.cc/technologies/single-use-bioprocessing/), [Sterile fill-finish and lyophilisation](https://onco.cc/technologies/sterile-fill-finish/)
- drugs: [Autogene cevumeran](https://onco.cc/drugs/autogene-cevumeran/), [Intismeran autogene](https://onco.cc/drugs/intismeran-autogene/)
- companies: [Aldevron (Danaher)](https://onco.cc/companies/aldevron/), [BioNTech](https://onco.cc/companies/biontech/), [Lonza](https://onco.cc/companies/lonza/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Moderna](https://onco.cc/companies/moderna/), [Thermo Fisher Scientific](https://onco.cc/companies/thermo-fisher/), [Touchlight](https://onco.cc/companies/touchlight/)

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