title: Aptamer Affinity Maturation by Resampling and Microarray Selection.
abstract: Aptamers have significant potential as affinity reagents, but better approaches are critically needed to discover higher affinity nucleic acids to widen the scope for their diagnostic, therapeutic, and proteomic application. Here, we report aptamer affinity maturation, a novel aptamer enhancement technique, which combines bioinformatic resampling of aptamer sequence data and microarray selection to navigate the combinatorial chemistry binding landscape. Aptamer affinity maturation is shown to improve aptamer affinity by an order of magnitude in a single round. The novel aptamers exhibited significant adaptation, the complexity of which precludes discovery by other microarray based methods. Honing aptamer sequences using aptamer affinity maturation could help optimize a next generation of nucleic acid affinity reagents.
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR China.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Kinghorn
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR China.
authors.forename: Roderick M
authors.initials: RM
authors.lastname: Dirkzwager
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR China.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Liang
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR China.
authors.forename: Yee-Wai
authors.initials: YW
authors.lastname: Cheung
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR China.
authors.forename: Lewis A
authors.initials: LA
authors.lastname: Fraser
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR China.
authors.forename: Simon Chi-Chin
authors.initials: SC
authors.lastname: Shiu
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR China.
authors.forename: Marco S L
authors.initials: MS
authors.lastname: Tang
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Pokfulam, Hong Kong SAR China.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Tanner
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010963:Plasmodium falciparum; D052156:SELEX Aptamer Technique / Q000379:methods
chemical_list: D052157:Aptamers, Nucleotide; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1