oa Editorial [Hot topic: Baculovirus: A Promising Vector for Gene Therapy? (Guest Editor: Yu-Chen Hu)]

The widely used viral gene therapy vectors include retrovirus, lentivirus, adenovirus and adeno-associated virus, which have proven to be clinically valuable in numerous trials. These vectors, however, possess respective drawbacks and may raise safety concerns [1] although recent clinical trials have shown encouraging results [2]. Moreover, the production of these vectors has posed challenges in large scale production. In contrast to the commonly employed viral vectors, baculovirus is an insect virus and has been extensively employed for recombinant protein production by infecting its natural host insect cells since 1980s. However, two groups in the mid-1990s uncovered that baculovirus can enter mammalian cells and mediate transgene expression as long as the transgene is driven by a promoter active in mammalian cells [3,4]. Since then, following studies have demonstrated that baculovirus can efficiently transduce cells originating from human, rodent, porcine, bovine, rabbit, fish and avian species [5]. Baculovirus also transduces dividing and nondividing cells as well as primary cells including mesenchymal stem cells [6] and embryonic stem cells [7]. In mammalian cells, baculovirus neither replicates nor imposes apparent cytotoxicity, hence minimizing the possible side effects. Also baculovirus is non-pathogenic, hence the handling and production can be carried out in biosafety level 1 laboratories. Baculovirus is easy to construct and produced to high titers and can accommodate a single large insert or multiple genes encompassing the regulatory elements [5,8,9]. These findings and attributes have fueled the interests to explore baculovirus as a vector for gene therapy and a plethora of emerging applications. In this special issue, 3 papers review the development of baculovirus vectors for in vitro applications including cell-based assay development for drug screening [10], display of eucaryotic proteins [11] and recombinant protein production [12]. Baculovirus has been used for in vivo gene delivery, hence its in vivo applications and monitoring are crucial and reviewed in this issue [13]. Inspired by the accumulation of more fundamental knowledge and discovery of new permissive cell types, baculovirus has also been exploited in emerging fields such as cancer therapy [14], vaccine development [15] and tissue regeneration [16], which are reviewed by Madhan et al., Wang and Balasundaram, and Lin et al., respectively. Due to the mounting interests and applications, whether baculovirus is truly safe and what immune responses are provoked after baculovirus transduction of cells or administration into animals have emerged as an important issue, which is reviewed by Abe and Matsuura [17]. Finally, the translation of baculovirus technology from bench to bedside hinges critically on whether the baculoviral vectors can be produced and purified in large scale at reasonable cost, therefore, the bioprocessing of baculoviral vectors is reviewed by Aucoin et al. [18]. Compared to other well-known viral vectors, the development of baculoviral vector for gene delivery is still in its infancy. To date baculovirus-mediated gene therapy remains unknown to a large population of scientific community and has yet to advance to clinical trials. Nevertheless, the potential of baculovirus has attracted a rapidly increasing number of research groups to enter this field, with research topics covering the fundamental virology studies, viral vector development, new applications, to downstream production and purification. Although more needs to be done to elucidate and ameliorate the safety profile and efficacy, it is anticipated that this technology will yield dividends in coming years.