Efficient gene transfer by fiber-mutant adenoviral vectors containing RGD peptide

• Published in: Biochimica et biophysica acta 2001-11, Vol.1568 (1), p.13-20
• Main Authors: Koizumi, Naoya, Mizuguchi, Hiroyuki, Hosono, Tetsuji, Ishii-Watabe, Akiko, Uchida, Eriko, Utoguchi, Naoki, Watanabe, Yoshiteru, Hayakawa, Takao
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus vector; Animals; Cell Line; Fiber; Gene therapy; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Integrins - analysis; Mice; Oligopeptides - genetics; Receptors, Virus - analysis; Receptors, Vitronectin - analysis; Retargeting; Tumor Cells, Cultured
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/S0304-4165(01)00194-5

One of the hurdles to adenovirus (Ad)-mediated gene transfer is that Ad vectors mediate inefficient gene transfer into cells lacking in the primary receptors, Coxsackievirus and adenovirus receptor (CAR). We previously developed a fiber-mutant Ad vector containing the Arg-Gly-Asp (RGD)-containing peptide motif on the HI loop of the fiber knob, and showed that the mutant vector had enhanced gene transfer activity to human glioma cells, which showed little CAR expression, compared to the vector containing wild type fiber. In this study, the feasibility of the Ad vector containing RGD peptide on the fiber knob was examined in a wide variety of cell types: CAR-positive or -negative human tumor cells, mouse cells, and leukemia cells. The mutant vector infected the cells, which lacked CAR expression but showed αv integrin expression, about 10–1000 times more efficiently than the vector containing wild type fiber via an RGD-integrin (αvβ3 and αvβ5)-dependent, CAR-independent cell entry pathway. The results of this study indicate that Ad vector containing RGD peptide on the fiber knob could be of great utility for gene therapy and gene transfer experiments.