title: Baculoviruses deficient in ie1 gene function abrogate viral gene expression in transduced mammalian cells.
abstract: One of the newest niches for baculoviruses-based technologies is their use as vectors for mammalian cell transduction and gene therapy applications. However, an outstanding safety issue related to such use is the residual expression of viral genes in infected mammalian cells. Here we show that infectious baculoviruses lacking the major transcriptional regulator, IE1, can be produced in insect host cells stably transformed with IE1 expression constructs lacking targets of homologous recombination that could promote the generation of wt-like revertants. Such ie1-deficient baculoviruses are unable to direct viral gene transcription to any appreciable degree and do not replicate in normal insect host cells. Most importantly, the residual viral gene expression, which occurs in mammalian cells infected with wt baculoviruses is reduced 10 to 100 fold in cells infected with ie1-deficient baculoviruses. Thus, ie1-deficient baculoviruses offer enhanced safety features to baculovirus-based vector systems destined for use in gene therapy applications.
authors: Insect Molecular Genetics and Biotechnology Group, Institute of Biology, National Centre for Scientific Research Demokritos, Aghia Paraskevi Attikis, Athens, Greece.
authors: Rodica
authors: R
authors: Efrose
authors: Luc
authors: L
authors: Swevers
authors: Kostas
authors: K
authors: Iatrou
mesh_terms: D000818:Animals; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015316:Genetic Therapy / Q000295:instrumentation*; D006801:Humans; D017874:Immediate-Early Proteins / Q000172:deficiency* / Q000235:genetics; D017924:Nucleopolyhedroviruses / Q000235:genetics / Q000378:metabolism*; D018411:Spodoptera; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: C069183:Ac-IE-1 protein, Autographa californica nucleopolyhedrovirus; D017874:Immediate-Early Proteins; D015534:Trans-Activators