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

Autor: Christopher McLendon, Kimberly Stewart, Yuan Wu, Thu Le Trinh, Cheng Cui, Sai Wang, Liqin Zhang, Myong-Sang Kim, Sena Cansiz, I-Ting Teng, Shuo Wan, Zunyi Yang, Kevin M. Bradley, Weijia Hou, Yuan Liu, Qunfeng Wu, Steven A. Benner, Shuichi Hoshika, Chen Liu, Diane J. Rowold, Weihong Tan
Rok vydání: 2016
Předmět:
Zdroj: Angewandte Chemie (International ed. in English), vol 55, iss 40
ISSN: 1433-7851
DOI: 10.1002/anie.201605058
Popis: Laboratory in vitro evolution (LIVE) might deliver DNA aptamers that bind proteins expressed on the surface of cells. Here, we use cell engineering to place on the surface of a liver cell line glypican 3 (GPC3), a possible marker for liver cancer diagnostics and theranostics. Libraries were then built from a six-letter genetic alphabet containing standard nucleobase and two added nucleobases (2-amino-8H-imidazo[1,2-a] [1,3,5] triazin-4-one and 6-amino-5-nitropyridin-2-one, trivially Z and P), Watson-Crick complements from an artificially expanded genetic information system (AEGIS). With counterselection against un-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.
Databáze: OpenAIRE