siRNA delivery via electropulsation: a review of the basic processes

Area of Science:

• Molecular Biology
• Biophysics
• Gene Therapy

Background:

• Small interfering RNAs (siRNAs) are potent tools for sequence-specific gene silencing in research and therapeutics.
• Efficient and targeted intracellular delivery of siRNAs remains a significant challenge for their clinical application.
• Current delivery methods often limit the full therapeutic potential of siRNA technology.

Purpose of the Study:

• To review the biophysical processes governing siRNA electrotransfer into cells using electropulsation (EP).
• To highlight EP as a method for efficient and viable siRNA delivery in vitro and in vivo.
• To discuss the potential of EP for clinical gene silencing applications.

Main Methods:

• Electropulsation (EP) applied to living cells for siRNA delivery.
• Analysis of biophysical principles including cell-size-dependent electropermeabilization and electrophoretic drag.
• Optimization of electrical parameters and pulsing buffers for controlled siRNA delivery and cell viability.

Main Results:

• EP facilitates direct cytoplasmic distribution of siRNA within cells.
• Preclinical studies demonstrate efficient silencing of targeted protein expression following EP delivery.
• EP allows for easy application directly to animals with minimal loss of cell viability.

Conclusions:

• Electropulsation is a viable physical method for targeted intracellular delivery of siRNAs.
• EP offers a controllable and efficient approach to gene silencing with promising preclinical results.
• EP represents a promising technology for advancing clinical applications of siRNA-based gene silencing.