Assessment of CFTR function after gene transfer in vitro and in vivo.
Cystic fibrosis (CF) a monogenic lethal disease and, therefore, ideally suited for the development of gene therapy. The first clinical trials were carried out shortly after cloning the CF gene in 1989. Since then, 25 trials have been carried out. Proof of principle for low-level airway gene transfer was established in most, but not all, trials. It is currently unclear whether current gene transfer efficiency will lead to improvements in clinically relevant endpoints such as inflammation or infection. In addition to addressing this important question, we and others are further improving airway gene transfer, by modifying existing and developing new gene transfer agents. Here, we describe pre-clinical methods related to assessing correction of the CF chloride transport defect.
Griesenbach
Uta
U
Department of Gene Therapy, Faculty of Medicine, Imperial College London,UK.
Munkonge
Felix M
FM
Sumner-Jones
Stephanie
S
Holder
Emma
E
Smith
Stephen N
SN
Boyd
A Christopher
AC
Gill
Deborah R
DR
Hyde
Stephen C
SC
Porteous
David
D
Alton
Eric W F W
EW
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002469:Cell Separation; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D012137:Respiratory System / Q000166:cytology; D014162:Transfection / Q000379:methods*
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D008156:Luciferases; D015056:1-Methyl-3-isobutylxanthine