Abstract: The invention provides for methods and compositions based on the expression of cellular levels of double-stranded RNA dependent kinase (PKR), an interferon-regulated gene, is used to enhance cancer cell death. The PKR gene is encoded by vectors, optionally containing specific promoters that are activated only in specific target cells. Cells producing PKR are treated with non-toxic, low doses of apoptosis-inducing agents, such as TNF-.alpha. or poly I:C, leading to programmed cell death without the use of conventional chemotherapeutic agents. Designing of recombinant viral vectors for gene therapy based on these expression systems for the treatment of human hepatitis B and C viruses, human papilloma virus, and other cancers and viral diseases is also taught.