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Messenger RNA

mRNA Theraputics Grpahic v2Manipulating gene expression with mRNA has several important advantages over viral DNA delivery.

• Lower risk of immune reactions
• Avoids 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


However, 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:

Lipid nanoparticle image
Lipid nanoparticle image
Polymer NPs and Micelles
Lipid nanoparticle image

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 conditions lead to highly reproducible mRNA lipid nanoparticles
Substantial material loss from low encapsulation efficiencyorangeRightArrowAchieve high mRNA encapsulation efficacy and potency
A labour-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 spkControl 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 BTEncapsulation efficiency (left) and particle size & PDI (right) were consistent between formulations with different mRNA lengths. Formulations were produced in triplicate on the NanoAssemblr Benchtop.

High Encapsulation Efficiency and Potency

high encapsFlow 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

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

How It Works


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 acidsinto the cytoplasmwhen vesicle pH decreases.

mRNA Resources


July 01, 2018

Robust low-volume production of nanoparticles for genetic manipulation of cells

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Publication - Abstract

April 26, 2018

Small Methods

State‐of‐the‐Art Design and Rapid‐Mixing Production Techniques of Lipid Nanoparticles for Nucleic Acid Delivery

Evers, M. J. W., Kulkarni, J. A., van der Meel, R., Cullis, P. R., Vader, P., & Schiffelers, R. M.

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Publication - Abstract

February 27, 2018

Cell Reports

A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing

J. Finn, A. Smith, M. Patel, L. Shaw, M. Youniss, J. Heteren, T. Dirstine, C. Ciullo, R. Lescarbeau, J. Seitzer, R. Shah...

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Publication - Abstract

June 15, 2018

Molecular therapy

Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis

E Robinson, KD MacDonald, K Slaughter, M McKinney

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Publication - Abstract

June 13, 2018

Journal of nucleic acids

SERPINA1 mRNA as a Treatment for Alpha-1 Antitrypsin Deficiency

B Connolly, C Isaacs, L Cheng, KH Asrani, R R Subramanian

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June 11, 2018

Rapid development and seamless scale-up of genetic nanomedicines

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