{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:41:06Z","timestamp":1784724066795,"version":"3.55.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute of Bioengineering and Bioimaging"},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["NRF-CRP17-2017-07"],"award-info":[{"award-number":["NRF-CRP17-2017-07"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Genetic alphabet expansion of DNA by introducing unnatural bases (UBs), as a fifth letter, dramatically augments the affinities of DNA aptamers that bind to target proteins. To determine whether UB-containing DNA (UB-DNA) aptamers obtained by affinity selection could spontaneously achieve high specificity, we have generated a series of UB-DNA aptamers (KD: 27\u2212182 pM) targeting each of four dengue non-structural protein 1 (DEN-NS1) serotypes. The specificity of each aptamer is remarkably high, and the aptamers can recognize the subtle variants of DEN-NS1 with at least 96.9% amino acid sequence identity, beyond the capability of serotype identification (69\u221280% sequence identities). Our UB-DNA aptamers specifically identified two major variants of dengue serotype 1 with 10-amino acid differences in the DEN-NS1 protein (352 aa) in Singaporeans\u2019 clinical samples. These results suggest that the high-affinity UB-DNA aptamers generated by affinity selection also acquire high target specificity. Intriguingly, one of the aptamers contained two different UBs as fifth and sixth letters, which are essential for the tight binding to the target. These two types of unnatural bases with distinct physicochemical properties profoundly expand the potential of DNA aptamers. Detection methods incorporating the UB-DNA aptamers will facilitate precise diagnoses of viral infections and other diseases.<\/jats:p>","DOI":"10.1093\/nar\/gkab515","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T11:42:15Z","timestamp":1622806935000},"page":"11407-11424","source":"Crossref","is-referenced-by-count":53,"title":["High-affinity five\/six-letter DNA aptamers with superior specificity enabling the detection of dengue NS1 protein variants beyond the serotype identification"],"prefix":"10.1093","volume":"49","author":[{"given":"Ken-ichiro","family":"Matsunaga","sequence":"first","affiliation":[{"name":"Institute of Bioengineering and Bioimaging, 31 Biopolis Way, The Nanos, #07-01, Singapore 138669, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Kimoto","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Bioimaging, 31 Biopolis Way, The Nanos, #07-01, Singapore 138669, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Weixun","family":"Lim","sequence":"additional","affiliation":[{"name":"National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Pen","family":"Tan","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Bioimaging, 31 Biopolis Way, The Nanos, #07-01, Singapore 138669, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u00a0Qian","family":"Wong","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Bioimaging, 31 Biopolis Way, The Nanos, #07-01, Singapore 138669, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Bioimaging, 31 Biopolis Way, The Nanos, #07-01, Singapore 138669, Singapore"},{"name":"Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Vasoo","sequence":"additional","affiliation":[{"name":"National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore"},{"name":"Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Dr., Experimental Medicine Building, Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Sin","family":"Leo","sequence":"additional","affiliation":[{"name":"National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore"},{"name":"Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Dr., Experimental Medicine Building, Singapore 636921, Singapore"},{"name":"Saw Swee Hock School of Public Health, National University of Singapore, 12 Science Drive 2, #10-01, Singapore 117549, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1115-8079","authenticated-orcid":false,"given":"Ichiro","family":"Hirao","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Bioimaging, 31 Biopolis Way, The Nanos, #07-01, Singapore 138669, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"2021111805165367900_B1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In vitro selection of RNA molecules that bind specific ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"2021111805165367900_B2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"2021111805165367900_B3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev-pharmtox-010716-104558","article-title":"Aptamers as Therapeutics","volume":"57","author":"Nimjee","year":"2017","journal-title":"Annu. 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