Title:Topical Application of In Vitro Transcribed mRNA to the Airways as a Novel Gene Therapy Approach for the Treatment of Cystic Fibrosis
Volume: 3
Issue: 2
Author(s): Shan Guan, Sarah M. Johler, Carsten Rudolph and Joseph Rosenecker*
Affiliation:
- Department of Pediatrics, University of Munich, Lindwurmstr. 2a, D-80337 Munich,Germany
Keywords:
IVT mRNA, cystic fibrosis, CF, CFTR, gene therapy, transcript therapy, airways, lung, in vitro, in vivo.
Abstract: 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.
