Baculovirus vectors: novel mammalian cell gene-delivery vehicles and their applications

Abstract

Various methods have been developed to transfer and express genes in mammalian cells. Each method, whether virally, non-virally, or physically-based, has unique favorable features, but also drawbacks with respect to meeting desired and specific needs. Baculoviruses have been used since 1983 to express recombinant genes controlled by strong insect-virus promoters in their natural host (insect) cells. Today this is a well-established and easy to handle system for producing large quantities of recombinant proteins for numerous purposes. In 1995 it was first published that recombinant baculoviruses are able to deliver genes into mammalian cells. These genes are expressed provided that they are controlled by a promoter which is active in mammalian cells. Since then, various vector variants have been developed and numerous potential and meaningful applications have been described. It is not surprising that the use of baculovirus vectors as mammalian cell gene delivery vectors is constantly increasing and that the system is undergoing permanent improvements. Based on the convenience of the system to transfer genes into mammalian cells, baculoviruses can be applied in cell-based assays for drug screening to overcome the long periods of time required to generate stable cell lines. Baculovirus vectors are able to deliver very large DNA sequences into mammalian cells and vectors for toxic gene products can also be generated. In addition, baculoviruses are valuable tools for launching viral infection in cases where there is no appropriate cell culture system. Moreover, recent research has shown that the vectors can be applied in vivo. Depending on the design of the study, baculovirus vectors allow for sustained gene expression or are able to induce an immune response directed against the delivered and/or displayed gene product. The latter offers the opportunity to generate monoclonal antibodies against certain proteins that have failed by other means. In addition, it points to the potential usefulness of baculovirus vectors as new kinds of vaccines. Baculovirus vectors are therefore considered an enabling technology for various product opportunities.