{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:56:42Z","timestamp":1791644202262,"version":"4.3.4"},"reference-count":20,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5884","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,6,27]]},"abstract":"<jats:p>As a result of the redundancy of the genetic code, adjacent pairs of amino acids can be encoded by as many as 36 different pairs of synonymous codons. A species-specific \u201ccodon pair bias\u201d provides that some synonymous codon pairs are used more or less frequently than statistically predicted. We synthesized de novo large DNA molecules using hundreds of over-or underrepresented synonymous codon pairs to encode the poliovirus capsid protein. Underrepresented codon pairs caused decreased rates of protein translation, and polioviruses containing such amino acid\u2013independent changes were attenuated in mice. Polioviruses thus customized were used to immunize mice and provided protective immunity after challenge. This \u201cdeath by a thousand cuts\u201d strategy could be generally applicable to attenuating many kinds of viruses.<\/jats:p>","DOI":"10.1126\/science.1155761","type":"journal-article","created":{"date-parts":[[2008,6,26]],"date-time":"2008-06-26T17:15:46Z","timestamp":1214500546000},"page":"1784-1787","source":"Crossref","is-referenced-by-count":638,"title":["Virus Attenuation by Genome-Scale Changes in Codon Pair Bias"],"prefix":"10.1126","volume":"320","author":[{"given":"J. Robert","family":"Coleman","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA."},{"name":"Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Papamichail","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA."},{"name":"Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Skiena","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA."},{"name":"Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Futcher","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA."},{"name":"Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckard","family":"Wimmer","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA."},{"name":"Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA."},{"name":"Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.10.3699"},{"key":"e_1_3_2_3_2","unstructured":"See supporting material on Science Online."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj488"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072266"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00738-06"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3259-3272.2006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.27.120193.002033"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.8.2330"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.8.3719-3730.2001"},{"key":"e_1_3_2_11_2","first-page":"463","year":"1994","unstructured":"S. Koike, in Cellular Receptors for Animal Viruses, E. Wimmer, Ed. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1994), pp. 463\u2013480.","journal-title":"Cellular Receptors for Animal Viruses"},{"key":"e_1_3_2_12_2","first-page":"377","volume":"2","year":"1909","unstructured":"K. Landsteiner, E. Popper, Z. Immun. Forsch. Orig.2, 377 (1909).","journal-title":"Z. Immun. Forsch. 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All authors declare that they have a patent pending relating to certain aspects of this work. Supported by NIH grants AI075219 and AI15122 (E.W.) and NSF grant EIA-0325123 (S.S.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1155761","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T05:07:34Z","timestamp":1704863254000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1155761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,27]]},"references-count":20,"journal-issue":{"issue":"5884","published-print":{"date-parts":[[2008,6,27]]}},"alternative-id":["10.1126\/science.1155761"],"URL":"https:\/\/doi.org\/10.1126\/science.1155761","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1117792.573872","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,27]]}}}