{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:27:42Z","timestamp":1790922462147,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2003,2,18]],"date-time":"2003-02-18T00:00:00Z","timestamp":1045526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Non\u2010viral vector\u2010mediated targeted gene repair could become a useful alternative to classical gene addition strategies. The methodology guarantees a physiologically regulated and persistent expression of the repaired gene, with reported gene conversion and phenotypic correction efficiencies approaching 40\u201350% in some <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models of disease. This is particularly important for cystic fibrosis (CF) because of its complex pathophysiology and the cellular heterogeneity of the cystic fibrosis transmembrane conductance regulator (<jats:italic>CFTR<\/jats:italic>) gene expression and function in the lung.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cell\u2010free biochemical assay was applied to assess the ability of CF airway epithelial cells to support chimeraplast\u2010mediated repair. In addition, a methodology allowing the relative quantification of the percentage of W1282X mutation repair in a heterozygous background using the PCR\/oligonucleotide ligation assay (PCR\/OLA) was developed. The performance of different chimeraplast and short single\u2010stranded oligonucleotide structures delivered by non\u2010viral vectors and electroporation was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chimeraplast\u2010mediated repair competency was corroborated in CF airway epithelial cells. However, their repair activity was about 5\u2010fold lower than that found in liver cells. Moreover, regardless of the corrector oligonucleotide structure applied to our CF bronchial epithelial cells, of compound heterozygous genotype (F508del\/W1282X), the percentage of their resulting wild\u2010type allele in the W1282X (exon 20) locus of the <jats:italic>CFTR<\/jats:italic> gene was not significantly different from that of the control untreated cells by our PCR\/OLA assay (confidence interval at 95% \u00b1 4 allele wild\u2010type).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Oligonucleotide\u2010mediated <jats:italic>CFTR<\/jats:italic> gene repair is an inefficient process in CF airway epithelial cells. Further improvements in oligonucleotide structure, nuclear delivery and\/or the capability for mismatch repair stimulation will be necessary to achieve therapeutic levels of mutation correction in these cells. 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