Cancer has proven to be an extremely difficult challenge to treat. Several fundamental issues currently underlie cancer treatment including differentiating self from non-self, functional coupling of the recognition and therapeutic components of various therapies, and the propensity of cancerous cells to develop resistance to common treatment modalities via evolutionary pressure. Given these limitations, there is a profound need to develop an all encompassing therapeutic that can uniquely target malignant cells, decouple recognition from treatment, and overcome cancer resistance. We describe herein, a new class of programmable self-assembling dsRNA-based cancer therapeutics that uniquely targets aberrant genetic sequences, and in a functionally decoupled manner, initiates a therapeutic polymerization cascade that induces apoptosis and immune activation. We further show that a DNA protector can be used to selectively seal the therapeutic RNA and induce specific and potent killing of cells containing the target oncogenic sequence, but not wildtype.