THE JOURNAL OF GENE MEDICINE RESEARCH ARTICLE J Gene Med 2009; 11: 302–312. Published online 4 February 2009 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/jgm.1299 Baculovirus transduction of chondrocytes elicits interferon-α/β and suppresses transgene expression Hsiao-Ping Lee 1 Yoshiharu Matsuura 2 Huang-Chi Chen 1 Yen-Lin Chen 3 Ching-Kuang Chuang 1 Takayuki Abe 2 Shiaw-Min Hwang 3 Hsiao-Chiao Shiah 1 Yu-Chen Hu 1 * 1 Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan 2 Research Centre for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan 3 Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan *Correspondence to: Yu-Chen Hu, Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan. E-mail: yuchen@che.nthu.edu.tw Received: 8 July 2008 Revised: 27 October 2008 Accepted: 22 December 2008 Abstract Background Baculovirus is an effective vector for gene delivery into primary chondrocytes and repeated baculovirus transduction (i.e. supertransduction) appears to be promising for prolonging transgene expression, but how supertransduction may influence baculovirus-mediated gene delivery is unknown. Methods We first investigated whether prior baculovirus transduction sup- pressed the ensuing transgene expression mediated by the supertransduced baculovirus, and then examined whether baculovirus triggered the expression of various cytokines. Whether interferon-α and -β (IFN-α/β ) suppressed the transgene expression as well as the pivotal step responsible for the attenuated transgene expression were examined. Results Baculovirus transduction of chondrocytes elicited an immediate yet transient expression of IFN-α/β , which repressed the transgene expression in a dose-dependent manner. The attenuation was observed for transgene expression driven by different promoters and resulted neither from internalization or nuclear import of baculovirus. Moreover, the attenuation was alleviated if supertransduction was performed when IFN-α/β responses diminished. Baculovirus transduction also triggered the expression of tumor necrosis factor-α and interleukin (IL)-6, but not IL-1β . Despite the induction of these responses, supertransduction of chondrocytes with a baculovirus expressing bone morphogenetic protein-2 successfully enhanced the chondrogenic differentiation and matrix synthesis. Conclusions Baculovirus transduction of primary chondrocytes elicits antiviral effects that suppress transgene expression. Nonetheless, baculovirus supertransduction comprises a feasible approach to extend transgene expression for cartilage engineering. Copyright  2009 John Wiley & Sons, Ltd. Keywords antiviral effects; baculovirus; chondrocytes; cytokine; interferon Introduction Weight-bearing articular cartilage comprises chondrocytes embedded in the extracellular matrix (ECM). The ECM consists of such molecules as col- lagens and glycosaminoglycans (GAGs) that impart the cartilage tensile strength and resistance to compression. Upon the occurrence of trauma, the structural integrity of cartilage may be disrupted but the ability of Copyright  2009 John Wiley & Sons, Ltd.