Biodistribution of AAV6.2-mCherry in C57BL/6J mouse dosed via nose-only inhalation route

In the past 7 years, the United States Food and Drug Administration (USFDA) has approved five Adeno-associated virus (AAV)-based gene therapy products treating a range of disorders and deadly monogenic diseases. Evaluation of appropriate cell targeting, laboratory personnel safety and overall vivarium containment is imperative for a successful delivery of aerosolized AAV gene therapy droplets to respiratory tract tissues in monogenic pulmonary diseases such as cystic fibrosis and α-1-antitrypsin (AAT) deficiency. The respiratory tract airway epithelium and epithelial cells in the lungs are suitable targets for the delivery of aerosolized particles, especially via the nose-only inhalation route of administration. In this study, we established a rodent nose-only AAV inhalation model for assessing the efficiency of administration, biodistribution and persistence of an AAV6.2 expressing a fluorescent protein, mCherry, 4 weeks after a single dose and evaluated the AAV aerosol containment during dosing.