Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

The Adenovirus Death Protein – A small membrane protein controls cell lysis and disease

Human adenoviruses (HAdVs) cause widespread acute and persistent infections. Infections are usually mild, and controlled by humoral and cell-based immunity. Reactivation of persistently infected immune cells can lead to a life-threatening disease in immuno-compromised individuals, especially children and transplant recipients. To date, no effective therapy or vaccine against HAdV disease is available to the public. HAdV species C type 2 and 5 are the best-studied of more than 100 HAdV types. They persist in infected cells and release their progeny by host-cell lysis to neighbouring cells and fluids, a process facilitated by the adenovirus death protein (ADP). ADP consists of about 100 amino acids and harbours a single membrane-spanning domain. It undergoes post-translational processing in ER and Golgi compartments, before localizing to the inner nuclear membrane. Here, we discuss the current knowledge on how ADP induces membrane rupture. Membrane rupture is essential for both progression of disease and efficacy of therapeutic viruses in clinical applications, in particular oncolytic therapy