DNA-Scaffolded Multivalent Ligands to Modulate Cell Function

• Published in: Chembiochem : a European journal of chemical biology 2014-06, Vol.15 (9), p.1268-1273
• Main Authors: Zhang, Zhiqing, Eckert, Mark A., Ali, M. Monsur, Liu, Linan, Kang, Dong-Ku, Chang, Elizabeth, Pone, Egest J., Sender, Leonard S., Fruman, David A., Zhao, Weian
• Format: Article
• Language: English
• Subjects: Antibodies - metabolism; Apoptosis; cancer; CD20; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA nanotechnology; Humans; Jurkat Cells; Ligands; Medical research; multivalency; Neoplasms - metabolism; Neoplasms - pathology; Receptors, Cell Surface - metabolism; rolling circle amplification; Signal Transduction; T cell receptors; Tumor Cells, Cultured
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201402100

We report a simple, versatile, multivalent ligand system that is capable of specifically and efficiently modulating cell‐surface receptor clustering and function. The multivalent ligand is made of a polymeric DNA scaffold decorated with biorecognition ligands (i.e., antibodies) to interrogate and modulate cell receptor signaling and function. Using CD20 clustering‐mediated apoptosis in B‐cell cancer cells as a model system, we demonstrated that our multivalent ligand is significantly more effective at inducing apoptosis of target cancer cells than its monovalent counterpart. This multivalent DNA material approach represents a new chemical biology tool to interrogate cell receptor signaling and functions and to potentially manipulate such functions for the development of therapeutics. On a roll: DNA molecules synthesized by rolling‐circle amplification can serve as simple polymeric scaffolds to interrogate and modulate cell‐receptor functions. We have demonstrated that our multivalent ligand can induce apoptosis of cancer cells more effectively than its monovalent counterpart; this represents a new approach for the development of therapeutics.