Engineering viral vectors for acoustically targeted gene delivery.

Autor: Li HR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Harb M; Department of Bioengineering, Rice University, Houston, TX, USA., Heath JE; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Trippett JS; Department of Bioengineering, Rice University, Houston, TX, USA., Shapiro MG; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA. mikhail@caltech.edu.; Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, USA. mikhail@caltech.edu.; Howard Hughes Medical Institute, Pasadena, CA, USA. mikhail@caltech.edu., Szablowski JO; Department of Bioengineering, Rice University, Houston, TX, USA. jszab@rice.edu.; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA. jszab@rice.edu.; Rice Neuroengineering Initiative, Rice University, Houston, TX, USA. jszab@rice.edu.; Rice Synthetic Biology Institute, Rice University, Houston, TX, USA. jszab@rice.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 10; Vol. 15 (1), pp. 4924. Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1038/s41467-024-48974-y
Abstrakt: Targeted 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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