Sonoporation: Gene transfer using ultrasound

Abstract

Genes can be transferred using viral or non-viral vectors. Non-viral methods that use plasmid DNA and short interference RNA (siRNA) have advantages, such as low immunogenicity and low likelihood of genomic integration in the host, when compared to viral methods. Non-viral methods have potential merit, but their gene transfer efficiency is not satisfactory. Therefore, new methods should be developed. Low-frequency ultrasound irradiation causes mechanical perturbation of the cell membrane, allowing the uptake of large molecules in the vicinity of the cavitation bubbles. The collapse of these bubbles generates small transient holes in the cell membrane and induces transient membrane permeabilization. This formation of small pores in the cell membrane using ultrasound allows the transfer of DNA/RNA into the cell. This phenomenon is known as sonoporation and is a gene delivery method that shows great promise as a potential new approach in gene therapy. Microbubbles lower the threshold of cavity formation. Complexes of therapeutic genes and microbubbles improve the transfer efficiency of genes. Diagnostic ultrasound is potentially a suitable sonoporator because it allows the real-time monitoring of irradiated fields.

Keywords: Cavity; Contrast agent; Diagnostic ultrasound; Gene therapy; Microbubbles.

Figure 1

Formation of cell membrane pores after ultrasound irradiation. Nucleic acid such as plasmids enters the cells through the membrane pores that are formed with ultrasound.

Figure 2

Microbubble response to an ultrasonic pressure wave. Microbubbles expand and contract when exposed to ultrasound at rarefaction and compression, respectively. At high pressure, microbubbles collapse and a shock wave is emitted.