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

摘要

We have proposed a novel technique to image and treat ovarian cancer with very high specificity, low background for imaging and low toxicity for therapy. We will make a riboswitch consisting of two aptamers and a sensor region that can hybridize with the specific intracellular ovarian cancer cell marker, VICKZ. The target for the first aptamer, EpCAM, is a surface antigen that is up-regulated in cancer cells. During cellular recycling, EpCAM will carry the attached riboswitch into the cell. Inside the cell, the riboswitch will interact with VICKZ mRNA. This interaction will change the conformation of the riboswitch to expose a second aptamer in the correct conformation to bind an administered radioactive agent which rapidly enters and exits the ovarian cancer cells, eg. antipyrine. Depending on the radioactive isotope attached to the agent, the ovarian cancer cells will be either imaged (123I) or killed (131I). We have successfully made both DNA and RNA aptamers to antipyrine, the 2nd proposed aptamer, and have been working on isolating aptamers to iodoantipyrine. We have also accomplished the important task of introducing a large portion of the eventual riboswitch into the cell interior where it appears to binds selectively to the target cancer cell marker, VICKZ mRNA.