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Related Concept Videos

Downstream Processing01:29

Downstream Processing

Downstream processing begins once fermentation is complete and involves a series of steps to recover and purify products such as acids, vitamins, antibiotics, or proteins.Cell HarvestingFor example, for intracellular protein-based products, the first step is harvesting the cells. This is typically achieved using centrifugation or filtration to separate the cells from the liquid phase.Cell Disruption for Intracellular ProductsIf the target product is intracellular, the harvested cells must be...

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Viscosity of concentrated mRNA solutions: Implications for downstream processing.

Amin Javidanbardan1, Fatemeh Najafi1, Ziqiao Wang1

  • 1Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.

Biotechnology Progress
|June 15, 2026
PubMed
Summary

Concentrated messenger RNA (mRNA) solutions exhibit significant viscosity, with larger self-amplifying RNA (saRNA) showing over 10x higher viscosity than firefly luciferase mRNA. This viscosity impacts downstream processing for mRNA therapeutics.

Keywords:
downstream processingmRNAsaRNAultrafiltrationviscosity

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Area of Science:

  • Biotechnology
  • Pharmaceutical Sciences
  • Materials Science

Background:

  • Messenger RNA (mRNA) therapeutics offer potential for treating infectious diseases, cancers, and genetic disorders.
  • Achieving therapeutic dosages requires concentrating mRNA, which can lead to significant solution viscosity.
  • Quantitative data on the viscosity of concentrated mRNA solutions is currently lacking.

Purpose of the Study:

  • To quantitatively measure the viscosity of concentrated messenger RNA (mRNA) solutions.
  • To analyze the behavior of mRNA viscosity under varying concentrations and shear rates.
  • To evaluate existing models for predicting mRNA solution viscosity.

Main Methods:

  • Experiments were conducted using two model mRNA constructs: firefly luciferase (Fluc) mRNA (2.117 kb) and self-amplifying RNA (saRNA) (9.442 kb).
  • Viscosity measurements were performed across a wide range of concentrations and shear rates (10–100 s⁻¹).
  • The obtained viscosity data were analyzed using established models from scientific literature.

Main Results:

  • The viscosity of the larger saRNA was over 140 mPa·s at 28 mg/mL, more than 10 times higher than Fluc mRNA under identical conditions.
  • mRNA solution viscosity demonstrated a weak dependence on shear rate, exhibiting some shear-thinning behavior.
  • Analysis using literature models provided insights into the physical properties governing mRNA solution viscosity.

Conclusions:

  • The study provides the first quantitative data on the viscosity of concentrated mRNA solutions.
  • Understanding mRNA viscosity is crucial for optimizing downstream processing and formulation of mRNA-based therapeutics.
  • The findings have implications for the scalable manufacturing and effective delivery of mRNA therapies.