Scientist Holding Small Formulation
Lipid Nanoparticles

Lipid nanoparticles (LNPs) are the most clinically advanced non-viral gene delivery system. Lipid nanoparticles safely and effectively deliver nucleic acids, overcoming a major barrier preventing the development and use of genetic medicines. Genetic medicine has many different applications such as gene editing, rapid vaccine development, immuno-oncology and treatment of rare genetic and undruggable diseases; all of which are usually hindered by nucleic acid delivery inefficiency.

Nucleic Acid Lipid Nanoparticle


Lipid nanoparticles offer many advantages over previous lipid-based nucleic acid delivery systems including:


• High nucleic acid encapsulation efficiency and potent
• Improved penetration into tissues to deliver therapeutics
• Low cytotoxicity and immunogenicity


These characteristics make lipid nanoparticles excellent candidates for nucleic acid delivery.


The first RNAi drug (Patisiran) uses lipid nanoparticles and is currently awaiting FDA approval.

Overcome Key Challenges in Advancing LNP Production

Challenges with Conventional Production Methods 

Solutions with the NanoAssemblr® Platform

The formulation process has significant batch-to-batch variabilityorangeRightArrowReproducible lipid nanoparticle manufacturing
Limited process control leads to lipid nanoparticle heterogeneityorangeRightArrowControlled manufacturing conditions result in homogeneous lipid nanoparticle formulations
Loading nanoparticles with nucleic acids are inefficientorangeRightArrowHigh nucleic acid loading efficiency in a one-step formulation process
Production is time-consuming and labor-intensiveorangeRightArrowRapid, effortless lipid nanoparticle production, and optimization
The manufacturing process is difficult to scale-uporangeRightArrowA seamless path to scaling up production

Key Benefits

A Reproducible Lipid Nanoparticle Manufacturing Process

Benchtop Independent ReproducibleLipid nanoparticle size was consistent for identical lipid composition formulated by three independent users.

Controlled Manufacturing Conditions Result in Homogeneous Lipid Nanoparticle Formulations

mRNA Scale-Up Cumulative Fractions
Hydrodynamic diameters and PDI were consistent between mRNA lipid nanoparticle fractions collected throughout the entire continuous flow manufacturing on the 8X Scale-Up System.

High Nucleic Acid Loading Efficiency in a One-Step Formulation Process 

Encapsulation Efficiency siRNA
siRNA-LNPs manufactured by three NanoAssemblr® instruments exhibited encapsulation efficiencies of higher than 95%.

A Seamless Path to Scaling Up LNP Production

siRNA Potency to Scale Up
Factor VII siRNA knockdown efficacy was maintained for nanoparticles produced on the NanoAssemblr® Benchtop, Blaze, and 8x Scale-Up.

NanoAssemblr® Technology Improves Lipid Nanoparticle Performance

The NanoAssemblr® Platform Generates a More Homogenous Nanoparticle Population

NanoAssemblr vs. T-Tube Homogenous
Particles generated by the NanoAssemblr® platform are more uniform than those made by conventional T-Tube mixing method.

NanoAssemblr®-Manufactured Lipid Nanoparticles Have a Homogenous Structure

NanoAssemblr vs. T-Tube Structure
T-tube generated lipid nanoparticles (left) exhibit a multilamellar morphology vs the homogeneous-core structure for the NanoAssemblr® generated lipid nanoparticles (right).

NanoAssemblr®-Manufactured Lipid Nanoparticles Exhibit Superior Knockdown Efficacy

NanoAssemblr vs. T-tube
Serum Factor VII siRNA knockdown efficacy was higher for NanoAssemblr® siRNA lipid nanoparticles compared to conventional T-tube lipid nanoparticles, 72 hours following systemic administration.

How It Works

LNP 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.

Get Started

To learn how Precision NanoSystems accelerates nanomedicine development from an idea to clinical applications, contact our Technical Sales Team.

Get in Touch

Lipid Nanoparticle 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 - Summary

November 21, 2018


Effective Lipidoid Nanoparticle Delivery In Vivo of siRNA Targeting Kappa Light Chain Production in a Murine Xenograft Model

Xun Ma, Ping Zhou, Adin Kugelmass, Denis Toskic, Melissa Warner, Lisa X. Lee, Teresa Fogaren, Ming Wang, Yamin Li, Liu Y...

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Publication - Abstract

November 01, 2018


Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced Synapse Loss by C1q Antibodies

Dejanovic, B., Huntley, M. A., De Mazière, A., Meilandt, W. J., Wu, T., Srinivasan, K., . . . Sheng, M.

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Publication - Abstract

October 29, 2018

Nature Communications

Cell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes

Nuphar Veiga, Meir Goldsmith, Yasmin Granot, Daniel Rosenblum, Niels Dammes, Ranit Kedmi, Srinivas Ramishetti & Dan Peer...

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