Provided in this application are formulations of double stranded RNA molecules and Krebs Cycle analogs that improving ribonuclease stability, reducing off-target effects of a double stranded siRNA molecule, or of reducing interferon responsiveness of a double stranded siRNA molecule using such dsRNA. Also disclosed are methods of treating a primary tumor or a metastasis by contacting circulating tumor cells, a primary tumor, or a metastasis with a described formulation.