Gene Delivery Systems for Broncho-alveolar Diseases

Period of Performance: 09/01/1998 - 08/31/1999


Phase 2 SBIR

Recipient Firm

Valentis, Inc.
Burlingame, CA 94010
Principal Investigator


Respiratory Syncytial Virus (RSV) infection in healthy older children and adults is usually localized to the upper respiratory tract. In certain disease populations, however (elderly patients with chronic cardiopulmonary disease, adults with chronic leukemia), RSV can cause life-threatening lower respiratory tract disease. We showed that cells transfected in vitro with a plasmid encoding for human AAT were resistant to infection with RSV. We reason that intracellular AAT inhibited maturation of RSV F protein and thus inhibited infectivity. The specific aim of this program, therefore, is to develop an AAT gene medicine, administered by inhalation, for the prevention of RSV infection. The target population for the AAT gene medicine would include the above-listed patients during the RSV season. Further, such a product, if shown safe and effective in children would likely be of benefit to pediatric populations with bronchopulmonary dysplasia or congenital heart disease. Inflammation is a significant component of many lung diseases including emphysema, cystic fibrosis, asthma, idiopathic pulmonary fibrosis and acute lung injury. The available data strongly suggest that delivery of the AAT gene so that it is expressed in lung epithelial cells would result in both antiproteolytic and anti- inflammatory activities. The use of AAT gene medicine could thus be rationally extended to these indications. PROPOSED COMMERCIAL APPLICATION: AAT gene medicine could be indicated as an anti-proteolytic and anti- inflammatory agent in the following lung diseases: RSV infection, emphysema, cystic fibrosis, idiopathic pulmonary fibrosis, acute lung injury and asthma.