Liquids in Dishes in a Lab
Messenger RNA

Manipulating gene expression with mRNA has several important advantages over viral DNA delivery.


 Lower risk of immune reactions


 Avoids the risk of permanent integration into the host genome


 Transient expression


These advantages make mRNA a desirable solution both in vitro and in vivo to express:


Therapeutic proteins and peptides


Vaccine antigens


Gene editing components such as Cas9, transposons, and other nucleases


mRNA Therapeutics Graphic


mRNA requires a delivery vehicle to protect against nucleases and facilitate cellular uptake and release into the cytoplasm. Lipid nanoparticles (LNPs) are the leading non-viral delivery system for mRNA that effectively solves several challenges facing mRNA delivery:


Protection from nucleases


Delivery and release into the cytoplasm


Laborious and time-consuming viral packaging


Safety concerns with viral vectors


Limitations in nucleic acid length with viral vectors.

Overcome Challenges in mRNA Delivery

Nanoparticle formulations offer a desirable alternative to viral delivery and with NanoAssemblr® technology, these formulations can be prepared on demand in seconds. Several nanoparticle formulations are being explored to package and deliver mRNA including:

Nucleic Acid Lipid Nanoparticle LNP
Polymeric Nanoparticle and Micelles
Polymer NPs and Micelles

Among these, nucleic acid-LNPs are the most clinically advanced. There are however challenges to producing mRNA-loaded nanoparticles that NanoAssemblr® technology addresses:

Challenges with Conventional Methods Benefits of NanoAssemblr® Technology
Limited control over particle sizeorangeRightArrowFine-tune particle size by changing formulation parameters
Significant batch-to-batch variabilityorangeRightArrowLaminar flow conditions lead to highly reproducible mRNA lipid nanoparticles
Substantial material loss from low encapsulation efficiencyorangeRightArrowAchieve high mRNA encapsulation efficacy and potency
A labor-intensive production process that is difficult to scale-uporangeRightArrowRapidly produce formulations for screening and optimization with a straightforward path to scale-up for clinical applications

Key Benefits


Fine-Tuning Particle Size by Changing Formulation Parameters

mRNA Size Tuning NanoAssemblr Spark


Control particle size by changing lipid:RNA ratio (top) and composition of lipids (bottom) among others. Size and PDI measured by dynamic light scattering from triplicate formulations produced using the NanoAssemblr® Spark.

Highly Reproducible mRNA LNP Formulations

mRNA Consistency BenchtopEncapsulation efficiency (left) and particle size & PDI (right) were consistent between formulations with different mRNA lengths. Formulations were produced in triplicate using the NanoAssemblr® platform.

High Encapsulation Efficiency and Potency

Encapsulation Efficiency & PotencyFlow cytometry showing expression of reporter protein GFP on primary rat cortical neurons 48h after in vitro treatment with mRNA-LNP.  GFP expression was dose-dependent with over 90% of cells expressing GFP at doses as low as 0.5 µg RNA per mL media. mRNA LNPs were produced on the NanoAssemblr® Spark.

Straightforward to Scale Production 


Consistent Results with the NanoAssemblr


Consistent results for size, encapsulation efficiency, composition and morphology achieved across the NanoAssemblr® Platform.

How It Works

mRNA Production and Delivery

1) An organic solvent containing dissolved lipids and an aqueous solution containing nucleic acids are injected into the two inlet channels of the NanoAssemblr® cartridge.
2) Under laminar flow, the two solutions do not immediately mix, but microscopic features engineered into the channel cause the two fluids to intermingle in a controlled and reproducible way.
3) Within a millisecond, the two fluids are completely mixed, causing a change in solvent polarity that triggers the self-assembly of lipid nanoparticles loaded with nucleic acids.

4) Changing the speed and ratio of fluid injection controls the size of the lipid nanoparticles.
5) Lipid nanoparticles mimic low-density lipoproteins, which allows them to be taken up by an endogenous cellular transport pathway to deliver nucleic acids to cells.
6) Using pH-sensitive lipids allow lipid nanoparticles to release encapsulated nucleic acids into the cytoplasm when vesicle pH decreases.

mRNA Resources

Application Note

March 15, 2022

Genome Editing of Human Primary T Cells with Lipid Nanoparticles

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Publication - Abstract

July 01, 2020

Journal of Controlled Release

Delivery of Self-amplifying mRNA Vaccines by Cationic Lipid Nanoparticles: The Impact of Cationic Lipid Select...

G. Lou, G. Anderluzzi, S.T. Schmidt, S. Woods, S. Gallorini, M. Brazzoli, F. Giusti, I. F...

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Publication - Abstract

May 08, 2020


Investigating the Impact of Delivery System Design on the Efficacy of Self-Amplifying RNA Vaccines

G. Anderluzzi, G. Lou, S. Gallorini, M. Brazzoli, R. Johnson, D.T. O'Hagan, B.C. Baudner a...

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Publication - Abstract

May 31, 2019


mRNA Vaccines Against H10N8 and H7N9 Influenza Viruses of Pandemic Potential Are Immunogenic and Well Tolerate...

R.A. Feldman, R. Fuhr, I. Smolenov, A. Ribeiro, L. Panther, M. Watson, J.J. Senn, M. Smith...

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Publication - Summary

May 17, 2019

Science Immunology

A Lipid-encapsulated mRNA Encoding a Potently Neutralizing Human Monoclonal Antibody Protects Against Chikungu...

N. Kose, J.M. Fox, G. Sapparapu, R. Bombardi, R.N. Tennekoon, A.D. de Silva, S.M. Elbashir...

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Publication - Summary

February 07, 2019

Nano Research

Chemotherapy Drugs Derived Nanoparticles Encapsulating mRNA Encoding Tumor Suppressor Proteins to Treat Triple...

C. Zhang, X. Zhang, W. Zhao, C. Zeng, W. Li, B. Li, X. Luo, J. Li, J. Jiang, B. Deng, D.W....

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