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Lipid Nanoparticles
Lipid nanoparticle imageLipid 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. Lipid nanoparticles offer many advantages over previous lipid-based nucleic acid delivery systems including:
• High nucleic acid encapsulation efficiency and potent
transfection
• 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 acid is 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


Indep BT users copyLipid 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 

EE Platofrm 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
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 NanoAssmblr platform generates a more homogenous nanoparticle population

NA vs T-tube siRNA LNP size
Particles generated by the NanoAssemblr platform are more uniform than those made by conventional T-Tube mixing method


NanoAssmeblr-manufactured lipid nanoparticles have a homogenous structure

NA vs T-tune TEM
T-tube generated lipid nanoparticles (left) exhibit a multilamellar morphology vs the homogeneous-core structure for the NanoAssmblr generated lipid nanoparticles (right).


NanoAssemblr-manufactured lipid nanoparticles exhibit superior knockdown efficacy

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

How It Works

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 acidsinto the cytoplasmwhen 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

Poster

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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Poster

June 11, 2018

Rapid development and seamless scale-up of genetic nanomedicines

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