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Many viruses and bacteria that once caused catastrophic pandemics (e.g., smallpox, poliomyelitis, measles, and diphtheria) are either eradicated or effectively controlled through routine vaccination programs. Nonetheless, vaccine manufacturing remains incredibly challenging. Viruses exhibiting high antigenic diversity and high mutation rates cannot be fairly contested using traditional vaccine production methods and complexities surrounding the manufacturing processes, which impose significant limitations. Virus\u2010like particles (VLPs) are recombinantly produced viral structures that exhibit immunoprotective traits of native viruses but are noninfectious. Several VLPs that compositionally match a given natural virus have been developed and licensed as vaccines. Expansively, a plethora of studies now confirms that VLPs can be designed to safely present heterologous antigens from a variety of pathogens unrelated to the chosen carrier VLPs. Owing to this design versatility, VLPs offer technological opportunities to modernize vaccine supply and disease response through rational bioengineering. These opportunities are greatly enhanced with the application of synthetic biology, the redesign and construction of novel biological entities. This review outlines how synthetic biology is currently applied to engineer VLP functions and manufacturing process. Current and developing technologies for the identification of novel target\u2010specific antigens and their usefulness for rational engineering of VLP functions (e.g., presentation of structurally diverse antigens, enhanced antigen immunogenicity, and improved vaccine stability) are described. When applied to manufacturing processes, synthetic biology approaches can also overcome specific challenges in VLP vaccine production. Finally, we address several challenges and benefits associated with the translation of VLP vaccine development into the industry.<\/jats:p>","DOI":"10.1002\/bit.26890","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T17:48:59Z","timestamp":1546278539000},"page":"919-935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Synthetic biology for bioengineering virus\u2010like particle vaccines"],"prefix":"10.1002","volume":"116","author":[{"given":"Hayley K.","family":"Charlton Hume","sequence":"first","affiliation":[{"name":"The University of Queensland, Australian Institute of Bioengineering and Nanotechnology St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6486-4762","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Vidigal","sequence":"additional","affiliation":[{"name":"Health &amp; Pharma Division, Animal Cell Technology Unit, Instituto de Biologia Experimental e Tecnol\u00f3gica (iBET) Oeiras Portugal"},{"name":"Health &amp; Pharma Division, Animal Cell Technology Unit, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica Oeiras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4550-4574","authenticated-orcid":false,"given":"Manuel J. 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