**1. Introduction**

660 Non-Viral Gene Therapy

[27] X. Huang; L.M. Bronstein; J. Retrum; C. Dufort; I. Tsvetkova; S. Aniagyei; B. Stein; G.

*7*, 2407.

Stucky; M. McKenna; N. Remmes; D. Baxter; C.C. Kao; B. Dragnea, *Nano Lett.*, 2007,

Dysregulated apoptosis plays a key role in the pathogenesis and progression of neoplastic disorders, allowing tumor cells to survive beyond their normal life-span, and to eventually acquire chemo-radioresistance (Laconi et al., 2000; Pommier et al., 2004). Thus, targeting either the intrinsic or the extrinsic pathways of apoptosis represent attractive therapeutic strategies for restoring apoptosis sensitivity of malignant cells, or activating agonists of apoptosis (Waxman & Schwartz, 2003). Due to the ability of death receptor ligands to induce cell death, there has been considerable interest in the physiological roles and therapeutic potential of these cytokines as anti-cancer agents. Death receptor ligands of the tumor necrosis factor α (TNFα) superfamily are type II transmembrane proteins that signal to target cells upon cell-cell contact, or after protease-mediated release to the extracellular space (Ashkenazi, 2002). Members of this family, including Fas ligand (FasL), TNFα, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), stand out because of their ability to induce cell death (Wajant, 2003; Wiley et al., 1995).
