GENE THERAPY FOR CYSTIC FIBROSIS USING CATIONIC LIPOSOME MEDIATED GENE TRANSFER

正常人CFTR转移到人CF上皮细胞，呼吸

Transfer of normal human CFTR to human CF epithelial cells, respiratory epithelium of CF mice, or human nasal airways (using adenoviral vectors) may lead to re-establishment of CFTR mediated chloride transport. Gene transfer mediated correction of the CF bioelectric defect in these model systems indicate the importance of investigating gene transfer-based protocols in the disease. In the present protocol, we evaluate a cationic liposome-based mechanism of delivery of normal CFTR to nasal respiratory epithelia of CF patients. Patients undergo one-time administration of a single dose of a lipid/DNA formulation containing DMRIE/DOPE (lipid) and plasmid DNA encoding the full length CFTR. To date, we have studied three patients and the results have been encouraging. Successful gene transfer was observed in two of three patients, and no evidence of toxicities or side effects were observed in the nasal airways, lung, or other organ systems. Because of these encouraging findings, we intend to study six additional patients in the near future.