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Plasmids
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 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:
Liposomes
Polymer NPs and Micelles
LNPs
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 size |  | Allowing fine-tuning of particle size by changing process parameters |
| Significant batch-to-batch variability | | Creating highly reproducible plasmid-lipid nanoparticles |
| Substantial material loss from low encapsulation efficiency | | Generating plasmid-lipid nanoparticles with high encapsulation efficacy and transfection potency |
| A labor-intensive production process that is difficult to scale-up | | Enabling 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.
Download the Full Poster
Download the Full Poster
Rapid, low-volume production of plasmid-LNP formulations
Plasmid Resources
Publication - Abstract
April 02, 2020
Journal of Controlled Release
Poster
July 01, 2018
Publication - Abstract
August 19, 2021
Publication - Abstract
March 12, 2021
Pharmaceutics
Publication - Abstract
November 15, 2020
pharmaceutics
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