Gene therapy to modify pulmonary host defenses.

Respiratory infections remain a significant public health problem and are presently the 6th leading cause of death in the United States. Antibiotic-resistant organisms are encountered increasingly in both community-acquired and nosocomial infections. Despite progress in antibiotic development, biological-response modifiers may have increasing application to augment pulmonary host defenses against either drug-resistant infections or in high-risk hosts. Toward this end, gene therapy proposes to deliver biologicals as nucleic acids rather than protein. Gene therapy has the potential advantage of targeting the biological to specific cells or tissue compartments, and a more favorable pharmacokinetic profile. Data on gene delivery and efficacy in preclinical models of pulmonary infection are presented and discussed.