Safety and efficacy of repetitive adenovirus-mediated transfer of CFTR cDNA to airway epithelia of primates and cotton rats.
Gene therapy for cystic fibrosis (CF) will require the safe transfer of CFTR cDNA to airway epithelia in vivo. We showed previously that a recombinant adenovirus, Ad2/CFTR-1, expresses CFTR in vitro. As adenovirus rarely integrates, treatment will require repeated vector administration. We applied Ad2/CFTR-1 to intrapulmonary airway epithelia of cotton rats and nasal epithelia of Rhesus monkeys. In both species we detected CFTR mRNA and protein after repeated administration and in monkeys, protein was detected six weeks after repeat administration. The vector did not replicate and was rapidly cleared. Despite an antibody response, there was no evidence of a local or systemic inflammatory response after repeat administration. These data indicate that repetitive administration of Ad2/CFTR-1 is both safe and efficacious.
Zabner
J
J
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
Petersen
D M
DM
Puga
A P
AP
Graham
S M
SM
Couture
L A
LA
Keyes
L D
LD
Lukason
M J
MJ
St George
J A
JA
Gregory
R J
RJ
Smith
A E
AE
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000008:administration & dosage* / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology; D012449:Safety; D016205:Sigmodontinae
C505032:CFTR protein, human; D017931:DNA Primers; D018076:DNA, Complementary; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator