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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 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:
LNPs
Liposomes
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 size |  | Fine-tune particle size by changing formulation parameters |
| Significant batch-to-batch variability | | Laminar flow conditions lead to highly reproducible mRNA lipid nanoparticles |
| Substantial material loss from low encapsulation efficiency | | Achieve high mRNA encapsulation efficacy and potency |
| A labor-intensive production process that is difficult to scale-up | | Rapidly produce formulations for screening and optimization with a straightforward path to scale-up for clinical applications |
Fine-Tuning Particle Size by Changing Formulation Parameters
Control particle size by changing lipid
Highly Reproducible mRNA LNP Formulations
Encapsulation 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
Flow 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 for size, encapsulation efficiency, composition and morphology achieved across the NanoAssemblr® Platform.
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
Publication - Abstract
July 01, 2020
Journal of Controlled Release
Publication - Abstract
May 08, 2020
Vaccines
Publication - Abstract
May 31, 2019
Vaccine
Publication - Summary
May 17, 2019
Science Immunology
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