Intravenous Delivery of pDNA and siRNA into Muscle with Bubble Liposomes and Ultrasound

Skeletal muscle is an attractive target tissue for numerous gene therapy strategies. Gene delivery into muscle has been extensively studied. Of the strategies, intravascular delivery of naked pDNA is desirable. Muscle has a high density of capillaries that are in close contact with myofibers. Previo...

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Bibliographic Details
Published in:ISTU 2009 2009-09, Vol.1215, p.299-302
Main Authors: Negishi, Yoichi, Sekine, Shohko, Endo, Yoko, Nishijima, Nobuaki, Suzuki, Ryo, Maruyama, Kazuo, Aramaki, Yukihiko
Format: Article
Language:English
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Summary:Skeletal muscle is an attractive target tissue for numerous gene therapy strategies. Gene delivery into muscle has been extensively studied. Of the strategies, intravascular delivery of naked pDNA is desirable. Muscle has a high density of capillaries that are in close contact with myofibers. Previously, we developed polyethylene glycol (PEG)-modified liposomes entrapping echo-contrast gas, known as ultrasound (US) imaging gas. We called the liposomes 'Bubble liposomes' (BLs). It has been reported that BLs improve the tissue permeability by cavitation on US exposure. Here, we modified the naked pDNA or siRNA transfer method into hind limb muscle through blood vessels using BLs and US. The intravenous delivery of pDNA intamuscle can be markedly enhanced when the pDNA is delivered in combination with BLs and US. In addition, the expression of pDNA is high in the US-focused site. Moreover, efficient gene delivery can be achieved by the intravenous delivery of pDNA into muscle with BLs and US. Expression is also down-regulated by delivering siRNA with BLs and US. Thus, this US-mediated BL technique involving veins may be an effective method for gene therapy.
ISSN:0094-243X