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DNA-scaffolded multivalent ligands to modulate cell function

  • Author(s): Zhang, Z
  • Eckert, MA
  • Ali, MM
  • Liu, L
  • Kang, DK
  • Chang, E
  • Pone, EJ
  • Sender, LS
  • Fruman, DA
  • Zhao, W
  • et al.
Abstract

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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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