Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids
Different strategies used in antitumor nucleic acid approaches. RNA-based strategies are commonly used to downregulate agents that are upregulated to favor cell proliferation or migration, such as Bcl-2. Alternatively, double stranded RNA (dsRNA) mimic polyinosinic-polycytidylic acid (pIC) can be used to engage the endosomal machinery, resulting in autophagy and apoptosis. Conversely, pDNA delivery aims at the expression of a protein that can (1) have toxic properties, directly causing tumor cell apoptosis (pDNA-based approaches); (2) be a chemokine, thus recruiting cell-mediated immunity; or (3) be a tumor antigen, recruiting humoral immunity (DNA vaccination-based strategies). Ultimately, all strategies aim at putting an end to tumor progression and eventually tumor cell destruction.