Use of a murine secreted alkaline phosphatase as a non-immunogenic reporter gene in mice.

Background: The development of any vector system as a gene delivery system requires its optimization in vitro and in vivo. Preliminary studies frequently involve the use of a reporter gene, which allows for the rapid and simple assay of vector function through monitoring expression levels of the reporter gene. However, evaluation of vector efficacy can be compromised by immune responses directed against immunogenic reporter proteins.

Cancer therapy utilizing an adenoviral vector expressing only E1A.

The human adenovirus type 5 (Ad5) early region 1A (E1A) proteins have been shown to have potent antitumor effects, due to their ability to reprogram oncogenic signalling pathways in tumor cells. The success of E1A antitumor therapy in animal models has led to its use in phase I and phase II clinical trials, where liposome-based delivery vehicles are being used to deliver a plasmid encoding E1A. To increase the efficiency of E1A delivery to tumors, we have developed an Ad vector deleted of all viral protein coding sequences (termed helper-dependent Ad vectors, hdAds) with the exception of E1A, designated hdAd-E1A.