Using the lung as a genetically engineered metabolic or catabolic factory to treat genetic diseases. Gene transfer to the lung can theoretically be used to treat two classes of disorders associated with either the absence of a functional protein product or the accumulation of a toxic metabolite in the circulation. In the case of hemophilia B, the lung can be used as a metabolic factory to secrete factor IX into the circulation. In contrast, diseases for which a toxic metabolic intermediate accumulates in the circulation might also be treated by pulmonary expression of an enzyme that degrades the harmful compound. For example, ornithine-delta-aminotransferase expression in the lung could be used to degrade circulating ornithine, which is present in excess in patients with gyrate atrophy and results in blindness.