title: Architecture of high-affinity unnatural-base DNA aptamers toward pharmaceutical applications.
abstract: We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. By this method, >80% of the remodeled DNA aptamer targeting interferon-γ (KD of 33 pM) survived in human serum at 37 °C after 3 days under our experimental conditions, and sustainably inhibited the biological activity of interferon-γ.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, Singapore 138669.|TagCyx Biotechnologies, 1-6-126 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, Singapore 138669.|TagCyx Biotechnologies, 1-6-126 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|PRESTO, JST, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kimoto
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute at Frederick, Frederick, MD, 21702 USA.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hanson
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute at Frederick, Frederick, MD, 21702 USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sanford
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute at Frederick, Frederick, MD, 21702 USA.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Young
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #04-01, Singapore 138669.|TagCyx Biotechnologies, 1-6-126 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirao
mesh_terms: D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D009690:Nucleic Acid Conformation; D017471:Receptors, Interferon / Q000378:metabolism; D052156:SELEX Aptamer Technique / Q000379:methods*
chemical_list: D052157:Aptamers, Nucleotide; D017471:Receptors, Interferon; D007371:Interferon-gamma