Proceedings of Annual Meeting of the Physiological Society of Japan
Proceedings of Annual Meeting of the Physiological Society of Japan
Session ID : 3PIA-016
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Direct in vivo Delivery of a Biologically Active Protein into Cardiomyocytes of Rats–The Development of the New Device for Protein Therapy–
*Atsutoshi HatadaKyoko MakabeYuji TsubotaHa CuiKen KohdaKen NakamuraKazunori YukawaYoshitaka OkamuraMasanobu Maeda
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Abstract
Background: In gene therapy, proteins are expressed about one week after injection and the degree of expression cannot be controlled. These disadvantages may be overcome by the in vivo delivery of biologically active proteins into cells. We investigated the possibility of targeted, direct in vivo protein transduction into cardiomyocytes by injecting β-galactosidase (β-gal) with hemagglutinating virus of Japan envelope (HVJ-E) vector into the left ventricular myocardium of rats.Methods: Male Wistar rats underwent left thoracotomy. We injected β-gal with HVJ-E vector (BH group), β-gal without the vector (B group), or the vector without β-gal (H group). The hearts were removed 1, 3, 6, 12 and 24 hours post-injection and each was cut in 5-μmthick slices with a cryostat. The sections were histochemically stained to detect β-gal enzymatic activity. β-gal-positive areas were present in these sections as β-gal activity, determined by computer-assisted colorimetric analysis.Results: The activity of β-gal in sections from rats injected with β-gal with HVJ-E vector was significantly stronger than those of β-gal without the vector and the vector without β-gal (p<0.01 at all time points).Conclusions: Our findings suggest that direct in vivo protein transduction into cardiomyocytes is possible. The type of targeted delivery system we present may have wide applications in the administration of therapeutic proteins to the heart. [J Physiol Sci. 2007;57 Suppl:S211]
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© 2007 The Physiological Society of Japan
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