{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:57:52Z","timestamp":1792173472057,"version":"4.4.0"},"reference-count":132,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Division of Intramural Research of the National Institute of Environmental Health Sciences","award":["ZIC ES102506-09"],"award-info":[{"award-number":["ZIC ES102506-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Engineered viral vectors designed to deliver genetic material to specific targets offer significant potential for disease treatment, safer vaccine development, and the creation of novel biochemical research tools. Viral tropism, the specificity of a virus for infecting a particular host, is often modified in recombinant viruses to achieve precise delivery, minimize off-target effects, enhance transduction efficiency, and improve safety. Key factors influencing tropism include surface protein interactions between the virus and host-cell, the availability of host-cell machinery for viral replication, and the host immune response. This review explores current strategies for modifying the tropism of recombinant viruses by altering their surface proteins. We provide an overview of recent advancements in targeting non-enveloped viruses (adenovirus and adeno-associated virus) and enveloped viruses (retro\/lentivirus, Rabies, Vesicular Stomatitis Virus, and Herpesvirus) to specific cell types. Additionally, we discuss approaches, such as rational design, directed evolution, and in silico and machine learning-based methods, for generating novel AAV variants with the desired tropism and the use of chimeric envelope proteins for pseudotyping enveloped viruses. Finally, we highlight the applications of these advancements and discuss the challenges and future directions in engineering viral tropism.<\/jats:p>","DOI":"10.3390\/ijms252011094","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T09:14:48Z","timestamp":1729242888000},"page":"11094","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Molecular Engineering of Virus Tropism"],"prefix":"10.3390","volume":"25","author":[{"given":"Bo","family":"He","sequence":"first","affiliation":[{"name":"Viral Vector Core, Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Wilson","sequence":"additional","affiliation":[{"name":"Viral Vector Core, Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-6903","authenticated-orcid":false,"given":"Shih-Heng","family":"Chen","sequence":"additional","affiliation":[{"name":"Viral Vector Core, Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kedar","family":"Sharma","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9100-0027","authenticated-orcid":false,"given":"Erica","family":"Scappini","sequence":"additional","affiliation":[{"name":"Fluorescent Microscopy and Imaging Center, Molecular and Cellular Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Cook","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Petrovich","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3166-8989","authenticated-orcid":false,"given":"Negin P.","family":"Martin","sequence":"additional","affiliation":[{"name":"Viral Vector Core, Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nomaguchi, M., Fujita, M., Miyazaki, Y., and Adachi, A. 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