Supplementary
Video 1. Intratracheal
aerosolization of viral vectors to newborn pig airways.
Video of bronchoscope
passing through vocal folds of the larynx and into the trachea. A 4-week-old
pig was sedated using isoflurane and intubated using a bronchoscope. The
bronchoscope was guided through vocal folds of the larynx to demonstrate
proper intubation. Tracheal rings visualized indicate that the trachea was
properly intubated.
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Article Abstract: Gene
therapy for airway diseases requires efficient delivery of nucleic acids to the
airways. In small animal models, gene delivery reagents are commonly delivered
as a bolus dose. However, large animal models are often more relevant for transition
from preclinical studies to human trials. Aerosolizing viral vectors to the
lungs of large animals can maximize anatomical distribution. Here we describe a
technique for aerosolization of viral vectors to the airways of newborn pigs.
Briefly, a pig is anesthetized, intubated with an endotracheal tube, and a
microsprayer is passed through the endotracheal tube. A fine mist is then
sprayed into the distal trachea. Widespread and uniform distribution of
transgene expression is critical for developing successful lung gene therapy
treatments.
Funding
This work was supported by the National Institutes of Health [NIH P01 HL-51670, NIH P01 HL-091842, NIH R01 HL-133089, NIH R01 HL-105821]; the Center for Gene Therapy of Cystic Fibrosis [NIH P30 DK-054759]; and the Cystic Fibrosis Foundation [SINN19XX0] and [COONEY18F0].