Complement-Mediated Selective Tumor Cell Lysis Enabled by Bi-Functional RNA Aptamers.

Unlike microbes that infect the human body, cancer cells are descended from normal cells and are not easily recognizable as "foreign" by the immune system of the host. However, if the malignant cells can be specifically earmarked for attack by a synthetic "designator", the powerful effector mechanisms of the immune response can be conscripted to treat cancer. To implement this strategy, we have been developing aptamer-derived molecular adaptors to invoke synthetic immune responses against cancer cells.

RNA aptamers targeted for human αA-crystallin do not bind αB-crystallin, and spare the α-crystallin domain.

The molecular chaperones, α-crystallins, belong to the small heat shock protein (sHSP) family and prevent the aggregation and insolubilization of client proteins. Studies in vivo have shown that the chaperone activity of the α-crystallins is raised or lowered in various disease states. Therefore, the development of tools to control chaperone activity may provide avenues for therapeutic intervention, as well as enable a molecular understanding of chaperone function.

Commandeering a biological pathway using aptamer-derived molecular adaptors.

Induction of molecular proximity can mediate a discrete functional response in biological systems. Therefore, creating new and specific connectivity between non-interacting proteins is a means of imposing rational control over biological processes. According to this principle, here we use composite RNA aptamers to generate molecular adaptors that link various 'target' molecules to a common 'utility' molecule, with the utility molecule being an entry point to a pathway conscripted to process the target molecule.