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In this\u00a0current study, we suggest a novel computational algorithm for generating live-attenuated vaccines via the introduction of silent mutation into regions that undergo selection for strong or weak local RNA folding or into regions that exhibit medium levels of sequence conservation. By implementing our approach to the ZIKV genome, we demonstrated\u00a0strong correlation between the degree of conserved RNA local energy disruption and replicative ability of the viruses in Vero cells. In\u00a0vivo analysis in the AG129 mouse model demonstrated the ability of the attenuated ZIKV strains to stimulate protective immune response against the wild-type virus. In some cases, up to 80% of the AG129 mice survived both the vaccination and the challenge with the\u00a0wild-type strains, while 0% of the nonvaccinated mice survived the challenge. Our study provides a blueprint for a computational design of live-attenuated vaccine strains that still preserve immunogenic epitopes of the original RNA viruses. We believe that the approach is generic and can be used successfully for additional viruses.<\/jats:p>","DOI":"10.1093\/nar\/gkae1313","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T07:25:34Z","timestamp":1735197934000},"source":"Crossref","is-referenced-by-count":3,"title":["Synthetic rational design of live-attenuated Zika viruses based on a\u00a0computational model"],"prefix":"10.1093","volume":"53","author":[{"given":"Modi","family":"Roopin","sequence":"first","affiliation":[{"name":"SynVaccine Ltd , Ramat Hachayal,\u00a03 Golda Meir Street, Science Park, Nes Ziona 7403648,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohar","family":"Zafrir","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Tel\u00a0Aviv University , Tel\u00a0Aviv,\u00a06139001,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bunpote","family":"Siridechadilok","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology , 113 Thailand Science Park, Paholyothin road, Klong Neung, Klong Luang Pathumthani 12120,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amporn","family":"Suphatrakul","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology , 113 Thailand Science Park, Paholyothin road, Klong Neung, Klong Luang Pathumthani 12120,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Julander","sequence":"additional","affiliation":[{"name":"Institute for Antiviral Research, Utah State University, E700 N955 , Logan , UT ,\u00a084322,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4194-7068","authenticated-orcid":false,"given":"Tamir","family":"Tuller","sequence":"additional","affiliation":[{"name":"SynVaccine Ltd , Ramat Hachayal,\u00a03 Golda Meir Street, Science Park, Nes Ziona 7403648,","place":["Israel"]},{"name":"Department of Biomedical Engineering, Tel\u00a0Aviv University , Tel\u00a0Aviv,\u00a06139001,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,11]]},"reference":[{"key":"2025020306165745100_B1","doi-asserted-by":"crossref","first-page":"e0004530","DOI":"10.1371\/journal.pntd.0004530","article-title":"Zika virus: medical countermeasure development challenges","volume":"10","author":"Malone","year":"2016","journal-title":"PLoS Negl. 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