Biotechnology and bioengineeringMar 24, 2026

Real-Time Tracking of mRNA Production in the Lab Using Raman Spectroscopy

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Raman spectroscopy with partial-least squares regression may enable real-time monitoring of nucleotide and mRNA concentrations during in vitro transcription.

Evidence

This mRNA manufacturing platform experiment simultaneously monitored ATP, CTP, GTP, UTP, and mRNA during IVT, with model R values of 0.82-0.99 and relative errors of 4%-13% compared with 10%-12% errors from offline reference assays.

Caveat

The evidence is a process-monitoring study, so the abstract supports manufacturing analytics rather than showing improved vaccine or therapeutic performance.

Simplified

The success of COVID-19 mRNA vaccines showcased the transformative potential of this adaptable, plug-and-play, and rapid response platform. Although these vaccines offer faster development and production compared to those traditionally produced in cell culture or eggs, critical manufacturing challenges remain. Notably, costly raw materials are required for in vitro transcription (IVT) and current methods for real-time monitoring of IVT are lacking. Herein, we present simultaneous inline monitoring of ATP, CTP, GTP, UTP, and mRNA concentrations during IVT using Raman spectroscopy and partial-least squares regression (PLS) data analysis. Model prediction performance resulted in Rof 0.82-0.99 and relative errors of 4%-13%, comparable to errors from reference offline assays (10%-12%). Furthermore, we analyze Raman spectral features associated with total mRNA concentration and sequence-specific variations, demonstrating sequence-independent prediction capability that eliminates the need for model recalibration across different products. This approach advances real-time monitoring for mRNA manufacturing and supports the future transition toward continuous processing, automated digital twins, and Pharma 4.0 paradigms. 2

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Real-Time Tracking of mRNA Production in the Lab Using Raman Spectroscopy

Abstract

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