Liquids in Dishes in a Lab

Plasmids are versatile constructs for regulating gene expression to treat or possibly cure diseases such as cancer and rare genetic disease. Plasmids can be instruments for several treatment modalities, offering longer-term effect than mRNA.


Once delivered to a cell, plasmids can produce:

• Small RNA that enters the RNAi pathway to downregulate gene expression
• Therapeutic proteins and peptides
• Gene editing components such as guide RNA, Cas9, transposons, and other nucleases

Fluorescence iPSC-NPCs 72h Plasmid
Fluorescence image of human iPSC-derived neuro progenitor cells expressing GFP 78h after treatment with plasmid-LNPs made with NanoAssemblr® Technology.

Overcome Challenges with Plasmid Delivery

Nanomedicines are being used to overcome challenges in delivering plasmids such as:

• Intracellular delivery
• Protection from nucleases
• Laborious and time-consuming viral packaging
• Safety concerns with viral vectors
• Limitations in plasmid length with viral vectors.

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 plasmids including:

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

Among these, nucleic acid-LNPs are the most clinically advanced. The first RNAi drug slated for approval (Patisiran) uses LNPs to deliver siRNA.


There are however challenges to producing plasmid-loaded nanoparticles that NanoAssemblr® technology addresses:

Challenges with Conventional Methods Benefits of NanoAssemblr® Technology
Limited control over particle sizeorangeRightArrowAllowing fine-tuning of particle size by changing process parameters
Significant batch-to-batch variabilityorangeRightArrowCreating highly reproducible plasmid-lipid nanoparticles
Substantial material loss from low encapsulation efficiencyorangeRightArrowGenerating plasmid-lipid nanoparticles with high encapsulation efficacy and transfection potency
A labor-intensive production process that is difficult to scale-uporangeRightArrowEnabling rapid production for screening and optimization and a straightforward path to scale-up for clinical applications

Plasmid-LNPs produced with NanoAssemblr® technology have been used to express exogenous genes in primary neurons, and human iPSC-derived neuro progenitor cells and neurons in vitro. Successful gene expression has also been demonstrated in brain and liver in animal models.

Case Study
Rapidly screening formulations for plasmid delivery in human neuro progenitor cells derived from induced pluripotent stem cells.
Multiple LNP formulations were rapidly produced on the NanoAssemblr® Spark and screened for expression of an encoded reporter gene in human iPSC-derived neuroprogenitor cells. Cell health (top) was determined by neurite length and reporter gene expression (bottom) was determined by GFP fluorescence at 6-hour intervals using an automated well plate imager. Formulations 3 and 4 were selected over 1 and 2 for further development on the basis of performance.

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Rapid, low-volume production of plasmid-LNP formulations

Rapid LNP Formulation Production

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Plasmid Resources


July 01, 2018

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

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Publication - Summary

January 06, 2019


Microfluidic manufacturing of surface-functionalized graphene oxide nanoflakes for gene delivery

R Di Santo, L Digiacomo, S Palchetti, V Palmieri, G Perini, D Pozzi, M Papi, G Caracciolo

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May 25, 2018

Multiple Myeloma

Microfluidic Production and Application of Lipid Nanoparticles for Nucleic Acid Transfection

A Thomas, SM Garg, RAG De Souza, E Ouellet, G Tharmarajah, D Reichert, M Ordobadi, S Ip, E C Ramsay

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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

April 18, 2018

Journal of Leukocyte Biology

Lipofection of Plasmid DNA into Human Mast Cell Lines using Lipid Nanoparticles Generated by Microfluidic Mixing

Duguay, B. A., Huang, K. W., & Kulka, M

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March 19, 2018

Advanced Drug Delivery Reviews

Advances in Microfluidics for Lipid Nanoparticles and Extracellular Vesicles and Applications in Drug Delivery Systems

M. Maekia, N. Kimurab,Y. Satoc, H. Harashimac, M. Tokeshi

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