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 |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cell engineering glypican 3 Aptamer aptamers cell engineering DNA Aptamers 010402 general chemistry 01 natural sciences Glypican 3 Article Catalysis Cell Line Mice 03 medical and health sciences Glypicans Genetics Animals Humans laboratory evolution Cell Engineering Cancer artificial nucleobases Base Sequence Clinical Laboratory Techniques Chemistry Liver cell Organic Chemistry Genetic systems General Medicine General Chemistry Aptamers Nucleotide Flow Cytometry Molecular biology 0104 chemical sciences Cell biology 030104 developmental biology Chemical Sciences Artificially Expanded Genetic Information System Alphabet Nucleotide Biotechnology Protein Binding |
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 |
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