We report gene transfer to the Edinburgh insertional mutant mouse (cf/cf), delivering CFTR cDNA-liposome complexes into the airways by nebulization. We show full restoration of cAMP related chloride responses in some animals and demonstrate, in the same tissues, human CFTR cDNA expression. Overall, a range of correction was seen with restoration of about 50% of the deficit between wild type mice and untreated cf/cf controls. We report modest correction in the intestinal tract following direct instillation and provide initial encouraging safety data for both the respiratory and intestinal tract following the liposome mediated gene delivery. The non-viral nature and potentially lower immunogenicity of DNA-liposomes suggest that this may offer a therapeutic alternative to adenoviral therapies.
Two synthetic peptides comprising an RGD moiety for intecase of the COS-7 and A375M cell lines. With the ECV304 grin binding and a polylysine moiety for DNA binding were cell line, optimum transfection occurred in the absence of tested for transfection efficiency under a variety of different chloroquine. Transfection efficiency of the peptides was conditions. Binding of target cells to the peptide was shown greatest at peptide:DNA ratios of 4:1 (w/w), which were to be strongly dependent on cyclisation of the peptides via calculated to generate complexes containing approxicysteine residues. Low (10 M) concentrations of chloromately 5000 peptide molecules per plasmid. This repquine, added to assist endocytic exit, unexpectedly resented approximately a 6:1 ratio of positive to negative reduced transfection efficiency in two of the cell lines charges. Peptide 5 was shown to have a higher transfectested, COS-7 and ECV304. However, transfection tion efficiency under most conditions, possibly because of efficiency increased at higher chloroquine concentrations more efficient stabilisation of cyclisation by two cysteineand exceeded that in the absence of chloroquine in the cysteine bonds.
In Fig. 1 a of this paper, the amino acid sequence of S. pombe at positions 34 (A) and 274 (V) are incorrect and should be Q and L respectively (single letter amino acid code). On the third page of this article (p. 241) the text in the first and second columns was transposed accidentally.
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