In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium

Melissa A. Rosenfeld, Kunihiko Yoshimura, Bruce C. Trapnell, Koichi Yoneyama, Eugene R. Rosenthal, Wilfried Dalemans, Masashi Fukayama, Joachim Bargon, Larue E. Stier, Leslie Stratford-Perricaudet, Michel Perricaudet, William B. Guggino, Andrea Pavirani, Jean Pierre Lecocq, Ronald G. Crystal

Research output: Contribution to journalArticlepeer-review

830 Scopus citations

Abstract

Direct transfer of the normal cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene to airway epithelium was evaluated using a replication-deficient recombinant adenovirus (Ad) vector containing normal human CFTR cDNA (Ad-CFTR). In vitro Ad-CFTR-infected CFPAC-1 CF epithelial cells expressed human CFTR mRNA and protein and demonstrated correction of defective cAMP-mediated Cl- permeability. Two days after in vivo intratracheal introduction of Ad-CFTR in cotton rats, in situ analysis demonstrated human CFTR gene expression in lung epithelium. PCR amplification of reverse transcribed lung RNA demonstrated human CFTR transcripts derived from Ad-CFTR, and Northern analysis of lung RNA revealed human CFTR transcripts for up to 6 weeks. Human CFTR protein was detected in epithelial cells using anti-human CFTR antibody 11-14 days after infection. While the safety and effectiveness remain to be demonstrated, these observations suggest the feasibility of in vivo CFTR gene transfer as therapy for the pulmonary manifestations of CF.

Original languageEnglish (US)
Pages (from-to)143-155
Number of pages13
JournalCell
Volume68
Issue number1
DOIs
StatePublished - Jan 10 1992

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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