Electrotransfer parameters as a tool for controlled and targeted gene expression in skin

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Dermatology

Background:

• Skin is a promising target for gene therapy due to its accessible cell types.
• Gene electrotransfer offers a method for delivering genetic material into skin cells.
• Optimizing electrotransfer parameters is crucial for effective gene delivery and therapeutic outcomes.

Purpose of the Study:

• To investigate how different electric pulse parameters in gene electrotransfer affect skin transfection.
• To control the depth, duration, and level of gene expression in the skin.
• To evaluate the local and systemic distribution of transgenes delivered via gene electrotransfer.

Main Methods:

• Utilized a multi-electrode array to apply controlled electric pulses (low and high voltage).
• Employed plasmids encoding a reporter gene (DsRed) to study transfection characteristics.
• Tested therapeutic gene plasmids (IL-12, shRNA against endoglin, shRNA against MCAM) in models of wound healing and melanoma.

Main Results:

• High-voltage pulses led to superficial skin transfection, local gene expression, and localized responses.
• Low-voltage pulses resulted in deeper skin transfection, prolonged gene expression, and increased transgene production.
• Low-voltage pulses showed potential for systemic transgene distribution.

Conclusions:

• Electric pulse parameters are critical for controlling gene electrotransfer outcomes in the skin.
• Tailoring electrotransfer settings is essential for optimizing therapeutic gene delivery for specific clinical applications.
• This research provides a foundation for translating gene electrotransfer into clinical practice for various skin conditions.