title: Selection and Characterization of DNA Aptamers Targeting All Four Serotypes of Dengue Viruses.
abstract: Dengue viruses (DENVs) are members of Flaviviridae family, which are associated with human disease. The envelope (E) protein plays an important role in viral infection. However, there is no effective antibody for clinical treatment due to antibody dependent enhancement of infection. In this study, using Systematic Evolution of Ligands by Exponential Enrichment (SELEX), we demonstrated the first aptamer (S15) that can bind to DENV-2 envelop protein domain III (ED3) with a high binding affinity. S15 was found to form a parallel quadruplex based on Quadfinder prediction, gel mobility assay and circular dichroism studies. Both the quadruplex structure and the sequence on 5'-end were necessary for the binding activity of S15. NMR titration experiments indicated that S15 bound to a highly conserved loop between βA and βB strands of ED3. Moreover, S15 can neutralize the infections by all four serotypes of DENVs. Our result provides a new opportunity in the development of DNA aptamers against DENVs in the future.
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Heng-Li
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Hsiao
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Hsiang-Chi
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Suh-Chin
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Jya-Wei
authors.initials: JW
authors.lastname: Cheng
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000737:chemistry; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D003715:Dengue / Q000276:immunology / Q000628:therapy / Q000821:virology; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics* / Q000276:immunology; D018604:Epitope Mapping; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D052156:SELEX Aptamer Technique; D017386:Sequence Homology, Amino Acid; D065288:Serogroup; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D052157:Aptamers, Nucleotide; D004279:DNA, Viral; D010446:Peptide Fragments; D014759:Viral Envelope Proteins