Shan Guan, Sarah M. Johler, Carsten Rudolph and Joseph Rosenecker* Pages 148 - 161 ( 14 )
Cystic fibrosis (CF) is a lethal congenital disease for which no efficient treatment exists currently. CF is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). After cloning of the CFTR gene, huge clinical interest has emerged in the transfer of the wild-type CFTR gene directly to the airways for the treatment of pulmonary disease. For this purpose a considerable number of viral and plasmid containing non-viral vectors have been developed, many clinical studies proved the concept of correcting the underlying chloride transport defect in CF patients. However, severe immune responses and low-efficient gene transfection hampered both approaches to be translated into routine clinical practices. The transfer of in vitro transcribed (IVT) mRNA for specific transgene expression could be used as an alternative approach once the challenges associated with IVT mRNA delivery were resolved. Apart from a brief overview of the development of gene therapy for CF in previous decades, the application of IVT mRNA as a potential novel therapy for CF treatment as well as their topical administration into the airways are discussed in this review.
IVT mRNA, cystic fibrosis, CF, CFTR, gene therapy, transcript therapy, airways, lung, in vitro, in vivo.
Department of Pediatrics, Ludwig-Maximilians University, 80337 Munich, Department of Pediatrics, Ludwig-Maximilians University, 80337 Munich, Department of Pediatrics, Ludwig-Maximilians University, 80337 Munich, Department of Pediatrics, University of Munich, Lindwurmstr. 2a, D-80337 Munich