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Aptamers against Cells Overexpressing Glypican 3 from Expanded Genetic Systems Combined with Cell Engineering and Laboratory Evolution
Author(s) -
Zhang Liqin,
Yang Zunyi,
Le Trinh Thu,
Teng ITing,
Wang Sai,
Bradley Kevin M.,
Hoshika Shuichi,
Wu Qunfeng,
Cansiz Sena,
Rowold Diane J.,
McLendon Christopher,
Kim MyongSang,
Wu Yuan,
Cui Cheng,
Liu Yuan,
Hou Weijia,
Stewart Kimberly,
Wan Shuo,
Liu Chen,
Benner Steven A.,
Tan Weihong
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201605058
Subject(s) - aptamer , systematic evolution of ligands by exponential enrichment , computational biology , directed evolution , cell , directed molecular evolution , dna , protein engineering , nucleobase , chemistry , glypican 3 , biology , biochemistry , genetics , cancer , rna , gene , mutant , enzyme
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‐8 H ‐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.