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We found that a virus bearing a deoptimized L-polymerase ORF evolved to escape temperature sensitivity restriction by mutations in L and multiple other proteins. Additional analysis revealed that single mutations in the M2-1 ORF were able to substantially escape the restriction imposed by the deoptimized polymerase. Based on this information, we generated a stable deoptimized RSV vaccine candidate with improved attenuation and immunogenicity suitable for additional development.<\/jats:p>","DOI":"10.1073\/pnas.1619242114","type":"journal-article","created":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T20:50:20Z","timestamp":1483476620000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":44,"title":["Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure"],"prefix":"10.1073","volume":"114","author":[{"given":"Cyril","family":"Le Nou\u00ebn","sequence":"first","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"McCarty","sequence":"additional","affiliation":[{"name":"RNA Viruses Section, Laboratory of 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