Automated production technologies for mRNA-based drugs

Schematische Darstellung der mRNA-Forschungsdienstleistungen

We offer end-to-end research services for your mRNA project! From DNA template development and custom mRNA design through in vitro production with optional modifications to scalable purification and comprehensive quality control. Through a extensive set of cell-free and cell-based systems, we validate the translatability and biological activity of your mRNA candidate.

You benefit from fast, efficient, and confidential workflows, high-throughput-­compatible screening, and GLP-compliant tests – enabling robust decisions and the targeted advancement of your mRNA drug candidates. Open for R&D collaboration and services.

Design of DNA templates

  • mRNA construct design and optimization at the DNA level:
    • Codon optimization
    • Flanking regulatory elements (5‘/3‘ UTRs)
    • Encoded poly(A) tail

Plasmid synthesis and linearization

  • Cloning strategies:
    • Restriction / ligation
    • Gibson assembly
    • Golden gate cloning
  • Endotoxin-free plasmid isolation from E. coli
  • Enzymatic linearization of plasmid DNA
  • Optional: PCR to generate linear template DNA

Co- and posttranscriptional modifications

  • Co-transcriptional capping
  • Incorporation of chemically modified nucleotides
  • Optional: Post-transcriptional addition of poly(A) tail
  • Phosphatase treatment

In vitro RNA production

  • In vitro transcription for mRNA generation:
    • Kit-based
    • Single component based
    • Use of optimized polymerases
    • Customized protocols applicable
    • Screening of different conditions in μL to mL scale possible

Purification

  • mRNA purification for μL scales:
    • Spin-column purification
    • Oligo(dT) bead purification
  • mRNA purification for mL scales:
    • Column chromatographic purification methods

Quality control

  • Concentration (UV / Vis)
  • Integrity (gel electrophoresis, bioanalyzer)
  • Identity (sequencing)
  • Purity:
    • ELISA / DotBlot for dsRNA
    • ELISA for enzyme residues
  • mRNA validation:
    • Rapid test for mRNA translatability 
    • in vitro mRNA translation in different lysate systems
    • Identify the ideal sequence and modifications for your drug candidates
    • Activity of the target protein
    • Endosomal Escape & Uptake-Analysis
  • Expression test in various cell types

Relevant publications

  • Kitte R, Rabel M, Geczy R, Park S, Fricke S, Koehl U, Tretbar US. Lipid Nanoparticles outperform Electro­poration in mRNA-based CAR T cell Engineering. Mol Ther Methods Clin Dev. 2023 Oct 18:31:101139. doi: 10.1016/j.omtm.2023.101139. eCollection 2023 Dec 14.
  • Kitte R, Serfling R, Blache U, Seitz C, Schrader S, Köhl U, Fricke S, Bär C, Tretbar US. Optimal chimeric antigen receptor (CAR)-mRNA for transient CAR T cell generation. Int J Mol Sci. 2025 Jan 23;26(3):965. doi: 10.3390/ijms26030965
  • Ye JL, Grieger K, Lu D, Brandenberger C, Juchem M, Jordan M, Oehlsen L, Zardo P, Werlein C, Hesse C, Sewald K, Tretbar S, Thum T, Chatterjee S, Bär C. Telomerase modRNA Offers a Novel RNA-Based Approach to Treat Human Pulmonary Fibrosis. Aging Cell. 2025 Nov;24(11):e70240. doi: 10.1111/acel.70240. Epub 2025 Sep 20.