Expression of ΔF508 CFTR in normal mouse lung after site-specific modification of CFTR sequences by SFHR

K. K. Goncz, A. Colosimo, B. Dallapiccola, L. Gagné, K. Hong, G. Novelli, D. Papahadjopoulos, T. Sawa, H. Schreier, J. Wiener-Kronish, Z. Xu, D. C. Gruenert

Research output: Contribution to journalArticlepeer-review


The development of gene targeting strategies for specific modification of genomic DNA in human somatic cells has provided a potential gene therapy for the treatment of inherited diseases. One approach, small fragment homologous replacement (SFHR), directly targets and modifies specific genomic sequences with small fragments of exogenous DNA (400-800 bp) that are homologous to genomic sequences except for the desired modification. This approach has been effective for the in vitro modification of exon 10 in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in human airway epithelial cells. As another step in the development of SFHR for gene therapy, studies were carried out to target and modify specific genomic sequences in exon 10 of the mouse CFTR (mCFTR) in vivo. Small DNA fragments (783 bp), homologous to mCFTR except for a 3-bp deletion (ΔF508) and a silent mutation which introduces a unique restriction site (Kpnl), were instilled into the lungs of normal mice using four different DNA vehicles (AVE, LipofectAMINE, DDAB, SuperFect). Successful modification was determined by PCR amplification of DNA or mRNA-derived cDNA followed by Kpnl digestion. The results of these studies showed that SFHR can be used as a gene therapy to introduce specific modifications into the cells of clinically affected organs and that the cells will express the new sequence.

Original languageEnglish
Pages (from-to)961-965
Number of pages5
JournalGene Therapy
Issue number12
Publication statusPublished - 2001


  • Cystic fibrosis
  • DNA delivery vehicles
  • Gene targeting
  • Gene therapy

ASJC Scopus subject areas

  • Genetics


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