Riboswitch-Mediated Aptamer Binding for Imaging and Therapy (RABIT): A Novel Technique to Selectively Target an Intracellular Ligand Specific for Ovarian Cancer

We have proposed to use a riboswitch to image or treat ovarian cancer. The riboswitch, attached to an EpCAM aptamer, will be transported into the cell where it will bind to VICKZ mRNA, a cancer cell marker, changing the conformation of the riboswitch so that it can bind to radioactive antipyrine. As a crucial first step we have selected both DNA and RNA aptamers to antipyrine and derivatives of antipyrine. We have also succeeded in showing ovarian cancer cell internalization and functional ability of a large portion of the proposed riboswitch. As an unanticipated byproduct of our work we have found that a DNA construct consisting of an EpCAM aptamer joined to an oligonucleotide complementary to VICKZ mRNA, which plays a key role in cell motility, was able to dramatically inhibit motility of ES2 ovarian cancer cells compared to untreated cells. A random DNA joined to the same EpCAM aptamer was unable to inhibit cell migration. These findings also demonstrate that we have accomplished the important task of introducing a large portion of the eventual riboswitch into the cell interior where it binds selectively to the target cancer cell marker.