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In the post-genome era, the analysis of disease-related genes has rapidly advanced, and the medical application of the information obtained from gene analysis is being put into practice. In particular, the development of a novel system to transfect the gene of interest selectively and efficiently into targeted cells is essential for the gene therapy of refractory diseases, in vivo functional analysis of genes, and establishment of animal models for diseases. However, a suitable carrier for selective gene delivery to targeted cells remains to be developed. The sonoporation method using microbubbles and ultrasound (US) exposure is one of the most promising approaches for effective gene transfection. However, it is difficult to transfect the therapeutic gene into the targeted organs/cells selectively by the conventional sonoporation method. Recently, our group has developed mannose-modified and US-responsive carriers/nucleic acid complexes (Man-PEG(2000) bubble lipoplexes), and succeeded in obtaining the enhanced and selective gene expression in mannose receptor-expressing cells by combination with US exposure. In this review, I described our gene transfection methods using Man-PEG(2000) bubble lipoplexes and external US exposure. Additionally, I also reviewed the enhancing mechanism of gene expression focusing on the intracellular transporting processes, in vivo distribution, and the activation of transcriptional factors. I believe that these findings help in the development of an effective gene transfection system using US-exposing system.

Development of Cell-selective Gene Transfection Method Using Sugar-modified and Ultrasound-responsive Liposomes