ABSTRACT

Adenoviral vectors represent a reliable and safe platform to transduce genes to target cells. The refinement of gene editing techniques allowed for a more sophisticated manipulation of the viral genome leading to new applications of adenoviruses. Among these, the deletion of genes involved in the replication cycle or the insertion of tissue-specific promoters made possible the generation of vectors that could discriminate between normal and malignant cells. Oncolytic adenoviruses can efficiently infect and lyse tumor cells in a specific manner. This results in the spreading

Abstract .................................................................................................................. 211 8.1 Introduction .................................................................................................. 212

8.1.1 Cancer ............................................................................................... 212 8.1.2 Current Therapies ............................................................................. 212

8.2 History of OAds ............................................................................................ 213 8.2.1 Oncolytic Adenoviruses.................................................................... 214

8.2.1.1 Exploiting the Lack of Cell Defense Mechanisms (Biological Targeting) ........................................................ 214

8.2.1.2 Cancer Promoter-Dependent OAds (Transcriptional Targeting) ........................................................................... 215

8.2.1.3 Armed OAd ........................................................................ 216 8.2.1.4 Capsid Modification of OAds (Transductional Targeting) .....218