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Published on: February 1, 2019
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.
Abstract:
Messenger RNA (mRNA) therapeutics can be used to protect against infectious disease and for the treatment of cancers and genetic disorders. In order to obtain the desired therapeutic dosage, it is necessary to concentrate the mRNA to levels where the viscosity of the mRNA solutions can become significant. However, there is currently no quantitative data on the viscosity of these concentrated mRNA solutions. Experiments were performed with two model mRNA constructs: a firefly luciferase (Fluc) mRNA (2.117 kb) and a self-amplifying RNA (9.442 kb) over a wide range of concentrations. The viscosity of the larger saRNA was more than 140 mPa·s at a concentration of 28 mg/mL, which is more than 10× larger than that for the Fluc mRNA under the same conditions. The viscosity was a weak function of shear rate (from 10 to 100 s-1), with some shear-thinning behavior. The viscosity data were analyzed using several available models from the literature, providing additional insights into the underlying physical behavior. The potential implications of the mRNA viscosity in the downstream processing of mRNA therapeutics are also discussed.
Insights
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.
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.
