Intrahepatic ultrasound-mediated gene delivery

Abstract

Transient ultrasound-induced increase in permeability of cell membrane and in some cases may enhance gene transfer. The objective of this work is to evaluate transfection efficiency and safety for intrahepatic gene delivery by sonoporation. Methods: Polyplexes of expression vector DNAs complexed to galactose-bearing polyethylenimine have been used. Expression vectors are two plasmid containing expression cassette for full size human preproinsulin gene controlled with CMV promoter and flanked by inverted terminal repeats of AAV (pTRhins) and the same cassette for marker gfp gene (pTRegfp). Animals were injected under US guidance with polyplexes in a dose of 40 mg pTRegfp/0.7 ml (rat) and of 15 mg pTRhins/0.15 ml (diabetic mouse) into the liver parenchyma of subdiaphragmal segments using 31 G needles. Afterwards injection locus in depth of 1 cm during 180 sec was insonated by 130 Db ultrasound using multifrequency 3–8 MHz probe.