Aptamers against Cells Overexpressing Glypican 3 from Expanded Genetic Systems Combined with Cell Engineering and Laboratory Evolution

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• 作者：Dr. Liqin Zhang ; Dr. Zunyi Yang ; Dr. Thu Le Trinh ; I-Ting Teng ; Sai Wang ; Kevin M. Bradley ; Dr. Shuichi Hoshika ; Dr. Qunfeng Wu ; Sena Cansiz ; Dr. Diane J. Rowold ; Christopher McLendon ; Myong-Sang Kim ; Yuan Wu ; Cheng Cui ; Yuan Liu ; Weijia Hou ; Kimberly Stewart ; Shuo Wan ; Prof. Dr. Chen Liu ; Prof. Dr. Steven A. Benner and Prof. Dr. Weihong Tan
• 刊名：Angewandte Chemie
• 出版年：2016
• 出版时间：September 26, 2016
• 年：2016
• 卷：128
• 期：40
• 页码：12560-12563
• 全文大小：2096K
• ISSN：1521-3757

文摘

Laboratory in vitro evolution (LIVE) might deliver DNA aptamers that bind proteins expressed on the surface of cells. In this work, we used cell engineering to place glypican 3 (GPC3), a possible marker for liver cancer theranostics, on the surface of a liver cell line. Libraries were then built from a six-letter genetic alphabet containing the standard nucleobases and two added nucleobases (2-amino-8H-imidazo[1,2-a][1,3,5]triazin-4-one and 6-amino-5-nitropyridin-2-one), Watson–Crick complements from an artificially expanded genetic information system (AEGIS). With counterselection against non-engineered cells, eight AEGIS-containing aptamers were recovered. Five bound selectively to GPC3-overexpressing cells. This selection–counterselection scheme had acceptable statistics, notwithstanding the possibility that cells engineered to overexpress GPC3 might also express different off-target proteins. This is the first example of such a combination.