Gene Therapy for Respiratory Viral Infections

Pulmonary infections by viruses may result in serious diseases of public health importance. The problems of the infections are exacerbated by rapid transmission of the pathogenic agents, which occur through inhalation and direct contact with contaminated surfaces. Moreover, cross-species transmission resulting from changes to viral genetic makeup poses a risk for emergence of pathogens with new characteristics, which in some cases may be responsible for causing different diseases. With the advent of efficient sequencing and nucleic acid-based virus-disabling technologies, gene therapy is well placed to advance new treatments to counter respiratory infections. Most studies aimed at using nucleic acids to treat respiratory viral infections have used RNA interference (RNAi) to silence viral gene targets. A few studies have used silencing of host factors required by the viruses as a means of inhibiting viral replication and preventing emergence of escape mutants. By administering antivirals to the airways, studies performed in vivo have taken advantage of the anatomy of the respiratory system to deliver therapeutic nucleic acids. Reported data have shown proof of principle of efficacy of gene therapy in models of respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus, influenza virus A, and measles virus, among others. RNAi-based gene therapy has been advanced to clinical trial for treatment of RSV infection. Although the primary endpoint was not met in an intent-to-treat analysis, the investigation has provided useful information for the advancement of gene therapy for current and emergent respiratory infections.