title: Gene and cell therapy for cystic fibrosis: from bench to bedside.
abstract: Clinical trials in cystic fibrosis (CF) patients established proof-of-principle for transfer of the wild-type cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelial cells. However, the limited efficacy of gene transfer vectors as well as extra- and intracellular barriers have prevented the development of a gene therapy-based treatment for CF. Here, we review the use of new viral and nonviral gene therapy vectors, as well as human artificial chromosomes, to overcome barriers to successful CFTR expression. Pre-clinical studies will surely benefit from novel animal models, such as CF pigs and ferrets. Prenatal gene therapy is a potential alternative to gene transfer to fully developed lungs. However, unresolved issues, including the possibility of adverse effects on pre- and postnatal development, the risk of initiating oncogenic or degenerative processes and germ line transmission require further investigation. Finally, we discuss the therapeutic potential of stem cells for CF lung disease.
authors.affiliation: Institute for the Experimental Treatment of Cystic Fibrosis, Milan, Italy. m.conese@unifg.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Conese
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Ascenzioni
authors.forename: A Christopher
authors.initials: AC
authors.lastname: Boyd
authors.forename: Charles
authors.initials: C
authors.lastname: Coutelle
authors.forename: Ida
authors.initials: I
authors.lastname: De Fino
authors.forename: Stefaan
authors.initials: S
authors.lastname: De Smedt
authors.forename: Joanna
authors.initials: J
authors.lastname: Rejman
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenecker
authors.forename: Dirk
authors.initials: D
authors.lastname: Schindelhauer
authors.forename: Bob J
authors.initials: BJ
authors.lastname: Scholte
mesh_terms: D000818:Animals; D022222:Chromosomes, Artificial, Human; D003550:Cystic Fibrosis / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends*; D005822:Genetic Vectors; D006801:Humans; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends*