Key result
Dexamethasone administration prior to high-dose systemic AAV9 injection significantly decreased transgene expression and vector genome copy number in the majority of murine tissues.
Why the study?
Glucocorticoids modulate vascular permeability and have been proposed to prevent liver toxicity during systemic AAV vector administration, but their impact on AAV vascular permeability after systemic injection was unclear.
Does dexamethasone impact the global transduction efficacy and vascular permeability of systemically administered AAV9 vectors in mice?
Population
Mice
Comparison
Dexamethasone treatment vs control
Design
Preclinical animal study
Authors
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Pre-dexamethasone may impair AAV9 transduction; leaves open optimal timing for human gene therapy trials.
Does dexamethasone impact the global transduction efficacy and vascular permeability of systemically administered AAV9 vectors in mice?
Dexamethasone inhibits AAV9 vascular permeability and decreases global transduction when administered prior to high-dose systemic AAV9, but this can be avoided by delaying dexamethasone administration until 2 hours post-vector injection.
Chai et al. (2019) studied this question. Dexamethasone vs. control mice was evaluated on Global transduction, vector biodistribution, and AAV vascular permeability. Dexamethasone administration prior to high-dose systemic AAV9 injection significantly decreased transgene expression and vector genome copy number in the majority of murine tissues.