Engineering viral vectors for acoustically targeted gene delivery

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dc.citation.articleNumber4924en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber15en_US
dc.contributor.authorLi, Hongyi R.en_US
dc.contributor.authorHarb, Manwalen_US
dc.contributor.authorHeath, John E.en_US
dc.contributor.authorTrippett, James S.en_US
dc.contributor.authorShapiro, Mikhail G.en_US
dc.contributor.authorSzablowski, Jerzy O.en_US
dc.contributor.orgRice Synthetic Biology Instituteen_US
dc.date.accessioned2024-08-07T19:15:02Zen_US
dc.date.available2024-08-07T19:15:02Zen_US
dc.date.issued2024en_US
dc.description.abstractTargeted gene delivery to the brain is a critical tool for neuroscience research and has significant potential to treat human disease. However, the site-specific delivery of common gene vectors such as adeno-associated viruses (AAVs) is typically performed via invasive injections, which limit its applicable scope of research and clinical applications. Alternatively, focused ultrasound blood-brain-barrier opening (FUS-BBBO), performed noninvasively, enables the site-specific entry of AAVs into the brain from systemic circulation. However, when used in conjunction with natural AAV serotypes, this approach has limited transduction efficiency and results in substantial undesirable transduction of peripheral organs. Here, we use high throughput in vivo selection to engineer new AAV vectors specifically designed for local neuronal transduction at the site of FUS-BBBO. The resulting vectors substantially enhance ultrasound-targeted gene delivery and neuronal tropism while reducing peripheral transduction, providing a more than ten-fold improvement in targeting specificity in two tested mouse strains. In addition to enhancing the only known approach to noninvasively target gene delivery to specific brain regions, these results establish the ability of AAV vectors to be evolved for specific physical delivery mechanisms.en_US
dc.identifier.citationLi, H. R., Harb, M., Heath, J. E., Trippett, J. S., Shapiro, M. G., & Szablowski, J. O. (2024). Engineering viral vectors for acoustically targeted gene delivery. Nature Communications, 15(1), 4924. https://doi.org/10.1038/s41467-024-48974-yen_US
dc.identifier.digitals41467-024-48974-yen_US
dc.identifier.doihttps://doi.org/10.1038/s41467-024-48974-yen_US
dc.identifier.urihttps://hdl.handle.net/1911/117612en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleEngineering viral vectors for acoustically targeted gene deliveryen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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