4.4 Article

DNA-Scaffolded Multivalent Ligands to Modulate Cell Function

Journal

CHEMBIOCHEM
Volume 15, Issue 9, Pages 1268-1273

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201402100

Keywords

cancer; CD20; DNA nanotechnology; multivalency; rolling circle amplification

Funding

  1. Department of Pharmaceutical Sciences at the Sue and Bill Gross Stem Cell Research Center
  2. Chao Family Comprehensive Cancer Center at University of California Irvine
  3. National Natural Science Foundation of China [51103179]
  4. Natural Science Foundation of Shandong Province, China [ZR2011BL017]
  5. Fundamental Research Funds for the Central Universities
  6. China Scholarship Council [CSC 201206455009]

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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.

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