Targeted Nucleoprotein Nanodevices for Diagnosis and Delivery

E. Singer, K. Munson, T. Wilson, S. Smith
Beckman Research Institute of the City of Hope, US

Keywords: bionanotechnology, ligand targeting, prostate cancer diagnosis, gene expression

Summary:

Mechanism-based covalent binding of DNA methyltransferase fusion proteins to synthetic DNA scaffolds permits the targeting of cells expressing fusion-ligand interacting proteins. Since the DNA scaffolds can be multivalent, cooperative binding enhances interaction of these nucleoprotein nanodevices with multi-subunit proteins. Divalent and trivalent nanodevices targeted with thioredoxin bind selectively to reactive stroma in prostate cancer specimens identifying the thioredoxin utilization system as a marker of the tumor microenvironment that can be used to distinguish prostate cancer from benign prostatic hyperplasia. Devices can be modified to deliver aptamers, gene expression cassettes, and DNA containing compounds (e. g. 2´-deoxyguanylurea) that can transfect cells or induce gene expression, epimutation, mutation, and fragile sites in targeted cells.