Engineering viral vectors for acoustically targeted gene delivery

dc.citation.articleNumber4924
dc.citation.journalTitleNature Communications
dc.citation.volumeNumber15
dc.contributor.authorLi, Hongyi R.
dc.contributor.authorHarb, Manwal
dc.contributor.authorHeath, John E.
dc.contributor.authorTrippett, James S.
dc.contributor.authorShapiro, Mikhail G.
dc.contributor.authorSzablowski, Jerzy O.
dc.contributor.orgRice Synthetic Biology Institute
dc.date.accessioned2024-08-07T19:15:02Z
dc.date.available2024-08-07T19:15:02Z
dc.date.issued2024
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.
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-y
dc.identifier.digitals41467-024-48974-y
dc.identifier.doihttps://doi.org/10.1038/s41467-024-48974-y
dc.identifier.urihttps://hdl.handle.net/1911/117612
dc.language.isoeng
dc.publisherSpringer Nature
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleEngineering viral vectors for acoustically targeted gene delivery
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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