Advances in adenoviral vectors: from genetic engineering to their biology

Abstract

Ad2 and Ad5 belong to a group of human cytolytic viruses that target the respiratory airways for reproduction, whereas latent infections establish within other tissues. Signals therefore exist that control this dichotomic process in different cell types, perhaps including cis and/or trans elements of viral origin. Since 1993, Ad2- and Ad5-based adenoviruses lacking all or part of the E1 regulatory region have been undergoing evaluation in phase I trials that target cancer and cystic fibrosis. These viruses are extremely attenuated and actually do not reproduce in most human cells. However, they retain most of the virus genetic program and often promote a significant cytotoxicity after infection, emphasizing the need to further cripple the virus biology to extend the duration of transgene expression, if required. We will review the strategies currently followed to engineer a professional lytic virus for epithelial cells into an innocuous gene delivery vehicle. Potential effects on the transducing properties of the vector that may result from the inactivation of viral activities that normally allow/regulate extrachromosomal gene expression during wild-type infection are discussed.

Profiling of genes which are differentially expressed in mouse liver in response to adenoviral vectors and delivered genes

“…Adenoviral vectors are known to cause an immune response 10 and a number of genes mediating the immune response, such as gamma interferon induced monokine (MIG), Stat1 and other interferon-induced genes are up-regulated in mice infected with the E1-deleted and CTGF vectors. Since high levels of TGF␤1 are known to suppress the induction of several genes which are involved in the immune response, 11 it is not surprising that these genes are not up-regulated in mice infected with the TGF␤1 expressing vector.…”

A binary adenoviral vector system for expressing high levels of the proapoptotic gene bax

“…1,2 Because of its high transduction efficiencies, adenoviral vector is useful in characterizing the functions and testing the therapeutic effects of a gene in vivo. Under most circumstances, constructing an E1-deleted adenoviral vector is quite straightforward.…”

Intra-articular adenoviral-mediated gene transfer of trail induces apoptosis of arthritic rabbit synovium

“…The recombinant adenoviral vector was derived from a replication-deficient type 5 adenovirus lacking the E1 and E3 loci. 28 The human TRAIL or the bacterial b-galactosidase cDNAs were inserted in place of the E1 region, and expression driven by the human cytomegalovirus immediate early promoter (CMV). Expression of TRAIL from the vector was confirmed by Western analysis following infection of HIG-82 cells and primary human synovial cells (Figure 1a).…”