Abstract
DDS technology required for an effective in vivo gene transfer depends on target disease. Important features are target cell-specificity, level, duration and cell number of gene expression following in vivo application. These features are determined not only by the ability of vectors used, but also by the nature of target cells, administration route, biodistribution, and interaction with components in the body. In this presentation, we report our approaches to improve in vivo gene transfer in two target cells: hepatocytes and myocytes. Targeted delivery of pDNA to hepatocytes was achieved by using galactose as a targeting ligand, but the level of gene expression might not be high enough even after boosting the expression with fusogenic peptides. Combined use of physical stimuli could be a solution. Muscle cells are easily transfected by direct injection of viral or nonviral vectors. However, direct injection results in gene expression only in limited cells adjacent to the injection site. For treatments of muscular dystrophies, gene expression in widespread myocytes is needed. To this end, gene delivery to myocytes in the diaphragm and hind legs was examined through intravascular injection of naked pDNA.
