. Inhaled gene products are desirable for chronic respiratory diseases with high morbidity and mortality, e.g. cystic fibrosis, emphysema, asthma, lung cancer, and tuberculosis. Aerosolization of DNA (plasmids) using conventional flow-through aerosol devices may cause breaking of plasmid strands due to extensive shearing. The investigators developed a prototype aerosol system (AERxTM) that generates a cloud of respirable aerosol by single extrusion of liquid through an array of precise micron- size holes. Nozzle and drug reservoir form an integral disposable part that avoids potentially toxic or incompatible stabilizers. Because the medicament is in its native form and enters the nozzle only once, the probability of damage to gene vectors is vastly reduced. The aerosol 'bolus' is released with a predetermined inspired volume to optimize delivery to desired parts of the respiratory system. Studies with normal volunteers showed that combining suitable particle size with breath and aerosol actuation control results in a desirable and reproducible pattern of drug deposition in the lung. Comprehensive in vitro evaluation of the aerosol properties and the quality of the aerosolized DNA/vector will be done in Phase I. In Phase II, the investigators plan to commence on clinical scale product development and pre clinical studies in a primate model.
