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Updated: Aug 13, 2026
09:41
Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
23.0K
Optimized microfluidic formulation and organic excipients for improved lipid nanoparticle mediated genome editing
Rohan Palanki1,2, Emily L Han1, Amanda M Murray1
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA. mjmitch@seas.upenn.edu.
Lab on a Chip
|July 22, 2024
Summary
Optimizing ionizable lipid nanoparticles (LNPs) enhances mRNA delivery for gene editing. This study developed a novel LNP formulation for effective CRISPR-Cas9 delivery to liver cells, promising new treatments for genetic diseases.
Area of Science:
- Biotechnology and Genetic Engineering
- Nanomedicine and Drug Delivery Systems
Background:
- mRNA-based gene editing holds significant therapeutic potential for genetic disorders.
- Effective and safe in vivo delivery of nucleic acid cargos is crucial for realizing this potential.
- Ionizable lipid nanoparticles (LNPs) are advanced non-viral RNA delivery systems, but require optimization for mRNA-based CRISPR-Cas9 platforms.
Purpose of the Study:
- To investigate the impact of microfluidic and lipid excipient parameters on LNP gene editing efficacy.
- To discover optimized LNP formulations for enhanced delivery of mRNA-based CRISPR-Cas9 systems.
Main Methods:
- Systematic screening of LNP formulations, varying phospholipid, cholesterol, and lipid-PEG structures.
- In vitro evaluation of gene editing efficiency in liver cells.
- In vivo assessment of therapeutic protein reduction using optimized LNP formulations.
Main Results:
- Distinct trends in LNP delivery efficacy were identified based on lipid excipient composition.
- A novel LNP formulation combining top-performing excipients demonstrated a 3-fold increase in in vitro gene editing.
- The optimized LNP formulation achieved a 3-fold greater reduction of a target protein in vivo compared to unoptimized formulations.
Conclusions:
- Systematic optimization of LNP formulation parameters is critical for enhancing gene editing delivery.
- A novel LNP formulation shows significant potential for targeted delivery of gene editors to the liver.
- This optimized LNP platform could be a valuable tool for treating metabolic and other genetic diseases.
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