Differences in gene expression between sonoporation in tumor and in muscle.
BACKGROUND
Ultrasound (US) is a novel and effective tool for the local delivery of genes into target tissues. US can temporarily change the permeability of a cell membrane and thus enhance the delivery of naked DNA into cells. In the present study, the efficiencies of gene expression mediated by US delivery in orthotopic liver tumor, subcutaneous tumor and muscle tissue were evaluated by changing the contrast agent concentrations and US exposure durations.


METHODS
Plasmid DNA coding for luciferase, interleukin-12 or enhanced green fluorescence protein was mixed with SonoVue and injected intratumorally or intramuscularly. The injection sites were then exposed to US (20% duty cycle and 0.4 W/cm(2) intensity).


RESULTS
The results obtained showed that the optimal condition was 50% SonoVue for tumors and 30% for muscle, with 10 min of US exposure. The expression levels of the transfected DNAs were in the order: muscle > subcutaneous tumor > orthotopic liver tumor.


CONCLUSIONS
The present study indicates that muscle tissue is a good target site for producing large amounts of gene products for the purpose of gene therapy.
Tsai
Kun-Che
KC
Institute of Biomedical Engineering, National Taiwan University College of Medicine, Taipei 100, Taiwan.
Liao
Zhe-Kang
ZK
Yang
Shu-Jyuan
SJ
Lin
Win-Li
WL
Shieh
Ming-Jium
MJ
Hwang
Lih-Hwa
LH
Chen
Wen-Shiang
WS
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002460:Cell Line; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000628:therapy; D008156:Luciferases / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D014463:Ultrasonography
D020533:Angiogenesis Inhibitors; D005456:Fluorescent Dyes; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; D008156:Luciferases