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These data indicate wider applicability to infectious disease and should encourage continued translation of <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\u2010based prophylactic vaccines into human clinical trials. At the conceptual level, <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\u2010based vaccines\u2014more than other genetic vectors\u2014combine the simplicity, safety, and focused immunogenicity of subunit vaccines with favorable immunological properties of live viral vaccines: (1) <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> vaccines are molecularly defined and carry no excess information. In the environment and upon physical contact, <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> is rapidly degraded by ubiquitous <jats:styled-content style=\"fixed-case\">RNases<\/jats:styled-content> and cannot persist. These characteristics also guarantee tight control over their immunogenic profile (including avoidance of vector\u2010specific immune responses that could interfere with repeated administration), pharmacokinetics, and dosing. (2) <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> vaccines are synthetically produced by an enzymatic process, just requiring information about the nucleic acid sequence of the desired antigen. This greatly reduces general complications associated with biological vaccine production, such as handling of infectious agents, genetic variability, environmental risks, or restrictions to vaccine distribution. (3) <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> can be tailored to provide potent adjuvant stimuli to the innate immune system by direct activation of <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010specific receptors; this may reduce the need for additional adjuvants. The formation of native antigen <jats:italic>in situ<\/jats:italic> affords great versatility, including intracellular localization, membrane association, posttranslational modification, supra\u2010molecular assembly, or targeted structural optimization of delivered antigen. Messenger <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> vaccines induce balanced immune responses including B cells, helper T cells, and cytotoxic T lymphocytes, rendering them an extremely adaptable platform. This article surveys the design, mode of action, and capabilities of state\u2010of\u2010the\u2010art <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> vaccines, focusing on the paradigm of influenza prophylaxis. <jats:italic>WIREs RNA<\/jats:italic> 2013, 4:737\u2013749. doi: 10.1002\/wrna.1189<\/jats:p><jats:p>This article is categorized under:\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Translation &gt; Translation Regulation<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA in Disease and Development &gt; RNA in Disease<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA Methods &gt; RNA Analyses in Cells<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wrna.1189","type":"journal-article","created":{"date-parts":[[2013,7,25]],"date-time":"2013-07-25T18:52:53Z","timestamp":1374778373000},"page":"737-749","source":"Crossref","is-referenced-by-count":45,"title":["Messenger <scp>RNA<\/scp>\u2010based vaccines: progress, challenges, applications"],"prefix":"10.1002","volume":"4","author":[{"given":"Thomas","family":"Kramps","sequence":"first","affiliation":[{"name":"BioNTech AG Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Probst","sequence":"additional","affiliation":[{"name":"IDT Biologika GmbH Dessau\u2010Rosslau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,25]]},"reference":[{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1028"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/erv.11.168"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"crossref","first-page":"D72","DOI":"10.1093\/nar\/gkn763","article-title":"Transterm: a database to aid the analysis of regulatory sequences in mRNAs","volume":"37","author":"Jacobs GH","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"e_1_2_7_1_6_1","volume-title":"Development Factory: Unlocking the Potential of Process Innovation","author":"Pisano GP","year":"1996"},{"key":"e_1_2_7_1_8_1","unstructured":"Jordan Report: Accelerated Development of Vaccines 2012. 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