Acharya Bishnu, Terao Shuji, Suzuki Toru, Naoe Michio, Hamada Katsuyuki, Mizuguchi Hiroyuki, Gotoh Akinobu
Laboratory of Cell and Gene Therapy, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663-8501; ; Advanced Medical Research Center, Hyogo University of Health Sciences, Hyogo 650-8530;
Exp Ther Med. 2010 May;1(3):537-540. doi: 10.3892/etm_00000085. Epub 2010 May 1.
The transduction efficacy of adenovirus serotype 5 (Ad5) vector in human renal carcinoma cells is generally low due to the down-regulated expression of Coxsackie and adenovirus receptor (CAR) in target cells. By contrast, the infectivity of adenovirus serotype 35 vectors depends on the binding rate to CD46 receptor, independent of CAR. In this study, we examined whether an adenovirus vector containing chimeric type 5 and type 35 fiber proteins (Ad5/F35) increases transduction efficiency compared to Ad5 vector in human renal carcinoma cells in vitro. The expression of CAR was much lower in the human renal carcinoma cells than in control HEK293 cells. By contrast, the expression of CD46 was similar and perhaps at a higher level in the human renal carcinoma cells than in the HEK293 cells. The transduction efficacy of Ad5/F35 vector was dramatically higher compared to that of Ad5 in human renal carcinoma cells, and was correlated to the expression of CD46. Thus, Ad5/35 vector may be useful for the development of novel gene therapy approaches to renal cell carcinoma.
由于靶细胞中柯萨奇病毒和腺病毒受体（CAR）的表达下调，5型腺病毒（Ad5）载体在人肾癌细胞中的转导效率通常较低。相比之下，35型腺病毒载体的感染性取决于与CD46受体的结合率，与CAR无关。在本研究中，我们检测了一种含有5型和35型嵌合纤维蛋白的腺病毒载体（Ad5/F35）与Ad5载体相比，在体外人肾癌细胞中是否能提高转导效率。人肾癌细胞中CAR的表达远低于对照HEK293细胞。相比之下，人肾癌细胞中CD46的表达与HEK293细胞相似，甚至可能更高。在人肾癌细胞中，Ad5/F35载体的转导效率比Ad5显著更高，且与CD46的表达相关。因此，Ad5/35载体可能有助于开发针对肾细胞癌的新型基因治疗方法。
