Air-assisted intranasal instillation enhances adenoviral delivery to the olfactory epithelium and respiratory tract

Intranasal instillation is used to deliver adenoviral vectors to the olfactory epithelium and respiratory tract. The success of this approach, however, has been tempered by inconsistent infectivity in both the epithelium and lungs. Infection of the epithelium may be hampered in part by the convoluted structure of the cavity, the presence of mucus or poor airflow in the posterior cavity. Delivery of adenovirus to the lungs can be uneven in the various lobes and distal bronchioles may be poorly infected. Current approaches to circumvent these issues rely principally on intubation or intratracheal instillation. Here we describe a technique that significantly improves adenoviral infectivity rates without requiring surgical intervention. We use compressed air to increase circulation of instilled adenovirus, resulting in enhanced infection in both the epithelium and lungs. This procedure is straightforward, simple to perform and requires no specialized equipment. In the epithelium, neurons and sustentacular cells are both labeled. In the lungs, all lobes can be infected, with penetration to the most distal bronchioles. The use of compressed air will likely also be useful for enhancing the distribution of other, desired agents within the epithelium, central nervous system and respiratory tract. Gene Therapy (2011) 18, 432-436; doi:10.1038/gt.2010.153; published online 18 November 2010