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DNA‐Scaffolded Multivalent Ligands to Modulate Cell Function
Authors:Prof. Dr. Zhiqing Zhang  Dr. Mark A. Eckert  Dr. M. Monsur Ali  Linan Liu  Dr. Dong‐Ku Kang  Elizabeth Chang  Dr. Egest J. Pone  Prof. Dr. Leonard S. Sender  Prof. Dr. David A. Fruman  Prof. Dr. Weian Zhao
Affiliation:1. State Key Laboratory of Heavy Oil Processing, College of Science, China University of Petroleum, 66 Changjiang (West) Rd, Huangdao, Qingdao, 266580 (P. R. China);2. Department of Pharmaceutical Sciences, Department of Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center and Chao Family Comprehensive Cancer Center, and Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA 92697 (USA) http://faculty.sites.uci.edu/zhaolab/;3. Department of Medicine, University of California, Irvine, Hyundai Cancer Institute, CHOC Children's Hospital, 1201 W. La Veta Avenue, Orange, CA 92697 (USA);4. Department of Molecular Biology & Biochemistry, University of California, 3242 McGaugh Hall, Irvine, CA 92697 (USA)
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.
Keywords:cancer  CD20  DNA nanotechnology  multivalency  rolling circle amplification
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