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Electroporation of Plasmid DNA into Mouse Skeletal Muscle
Published on: April 6, 2022
Numerical optimization of gene electrotransfer into muscle tissue.
Anze Zupanic1, Selma Corovic, Damijan Miklavcic
1University of Ljubljana, Faculty of Electrical Engineering, Trzaska cesta 25, SI-1000 Ljubljana, Slovenia.
Biomedical Engineering Online
|November 6, 2010
Summary
Optimizing gene electrotransfer in muscle tissue involves specific electrode distances, depths, and orientations. Numerical modeling guides selection of optimal voltages to maximize reversible electroporation and minimize tissue damage for effective gene therapy.
Area of Science:
- Biomedical Engineering
- Molecular Biology
Background:
- Electroporation facilitates pDNA transfer for gene therapy and DNA vaccination.
- Gene electrotransfer efficiency is influenced by electrode configuration and electric pulse parameters.
- Numerical modeling offers a rapid method for optimizing gene electrotransfer parameters.
Purpose of the Study:
- To determine optimal parameters for gene electrotransfer in muscle tissue using numerical modeling.
- To analyze the impact of electrode configuration and electric pulse parameters on electric field distribution.
Main Methods:
- A 3D muscle tissue model with two or six needle electrodes was developed.
- Parametric study and genetic algorithm optimization were used to assess electrode distances, insertion depths, orientation, and voltage.
- Solution quality was evaluated based on reversible/irreversible electroporation volumes and electric current.
Main Results:
- Large reversible electroporation volumes with minimal damage were achieved using greater electrode distances and insertion depths.
- Perpendicular electrode orientation to muscle fibers was superior for six electrodes; orientation had less impact with two electrodes.
- Optimal voltage windows were narrow, with higher voltages leading to irreversible electroporation.
Conclusions:
- This study presents the first numerical optimization of gene electrotransfer parameters at the tissue level.
- The generic modeling and optimization approach can be applied to various electrode configurations, pulsing protocols, and tissues.
- Numerical models can guide researchers and clinicians in selecting optimal in vivo gene electrotransfer parameters, potentially reducing animal use.
