Sonoselective delivery using ultrasound and microbubbles combined with intravenous rAAV9 CLDN5-GFP does not increase endothelial gene expression

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  • Rikke Hahn Kofoed
  • Elizabeth M. Simpson, University of British Columbia
  • ,
  • Kullervo Hynynen, Sunnybrook Research Institute, University of Toronto Faculty of Medicine
  • ,
  • Isabelle Aubert, Sunnybrook Research Institute, University of Toronto Faculty of Medicine

Transcranial ultrasound combined with intravenous microbubbles can be used to increase blood-brain barrier permeability or, at lower pressures, to mediate sonoselective gene delivery to endothelial cells. Previously, sonoselective gene delivery with plasmid-coated microbubbles as gene carriers resulted in transient transgene expression in the brain endothelium. We investigated the potential of recombinant adeno-associated virus 9 (rAAV9), a serotype known for its efficient transduction and long-term transgene expression, for sonoselective gene delivery to endothelial cells of the brain. We found that rAAV9 led to gene delivery to brain endothelial cells following intravenous administration at a dosage of 1 × 1011 GC/g. However, the sonoselective gene delivery approach with intravenous rAAV9, using the same parameters as previously used for plasmid delivery, did not increase transgene expression in brain endothelial cells targeted. These results suggest that intravenous rAAV9 are using mechanisms of entry into the cerebrovasculature that are not significantly influenced by sonoselective treatments known to facilitate endothelial cell entry of plasmids coated onto microbubbles.

Original languageEnglish
JournalGene Therapy
Publication statusPublished - 2023
Externally publishedYes

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© 2023, The Author(s), under exclusive licence to Springer Nature Limited.

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