Intratracheal (i.t.) and intravenous (i.v.) delivery of DNA-Expression using either mode of administration was maxivector formulations are two strategies to obtain gene transmal 24 h after injection and declined to around 10% of day fer to the lung. It is still uncertain, however, which of these 1 levels 2 weeks after injection. For i.v. delivery of DODAC: two modes of delivery will be more effective in the treat-DOPE-DNA complexes multilamellar vesicles were more ment of cystic fibrosis and other lung diseases. In this effective than large unilamellar vesicles in all organs invesstudy, we attempted to optimize formulations of the cationic tigated. Recombinant DNA could be detected in the distal liposome DODAC:DOPE (dioleoyldimethylammoniumlung region following either route of administration. Howchloride:dioleoylphosphatidylethanolamine) complexed to ever, i.t. administration predominantly led to DNA depoplasmids encoding chloramphenicol acetyltransferase for sition in epithelial cells lining the bronchioles, eg in clara i.t. and i.v. injection into CD-1 mice and compared the two cells, whereas i.v. administration resulted in DNA depomethods. Our results showed that both methods conferred sition in the alveolar region of the lung including type II reporter gene expression in the lung that was significantly alveolar epithelial cells. higher relative to injection of plasmid DNA alone.

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Cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain, with subunits originating both from the mitochondrial and nuclear genome. An eleven-year-old female presented initially with a seizure followed two months later with tonic-clonic seizures, weakness and aphasia. MRI of the cerebral hemispheres showed multiple infarcts. Previous history suggested gross and fine motor control deficits with learning difficulties. A muscle biopsy showed a specific decrease of COX staining in all fibres and pleomorphic mitochondria. Respiratory chain studies confirmed an isolated complex IV defect in muscle, whilst fibroblasts showed an initial COX activity below normal which rapidly came up to the normal range on culture. Sequencing of mtDNA revealed an heteroplasmic m.7023G>A mutation in the COX1 gene, with levels of 96% in muscle, 70% in blood and 50% in the initial skin fibroblast culture dropping to 10% in later passages. The mutation was present in a critical region of the COX1 gene, the V374M change being close to the two histidine residues His376 and His378 co-ordinating with the heme a and a (3), and His367 which co-ordinates a magnesium ion. This case highlights that a MELAS-like syndrome can occur with isolated COX deficiency.