Loading
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.
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.
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.
Query for this technology: (TITLE:"mRNA and lipid nanoparticle manufacturing" OR ABSTRACT:"mRNA and lipid nanoparticle manufacturing") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about mRNA and lipid nanoparticle manufacturing, not a curated reading list.
Shares Single-use bioprocessing systems, Thermo Fisher Scientific, Lonza, Sterile fill-finish and lyophilisation and the tag manufacturing-wave.
Shares Single-use bioprocessing systems, Cryopreservation and cell-therapy cold chain, Lonza and the tag manufacturing-wave.
Shares Thermo Fisher Scientific, Lonza and the tag manufacturing-wave.
Shares Single-use bioprocessing systems and the tag manufacturing-wave.
Shares Single-use bioprocessing systems and the tag manufacturing-wave.
Shares Lonza, Sterile fill-finish and lyophilisation and the tag manufacturing-wave.
Shares Sterile fill-finish and lyophilisation and the tag manufacturing-wave.
Shares Cryopreservation and cell-therapy cold chain and the tag manufacturing-wave.