Aerosol-mediated delivery of recombinant adenovirus to the airways of nonhuman primates.
At present, it is conceivable that gene therapy of the cystic fibrosis airway epithelium is possible using the direct transfer of a functional human cystic fibrosis transmembrane conductance regulator (CFTR) gene to a wide variety of patients' tracheo-bronchial cells. Here we describe a novel approach (aerosolization) to deliver a replication-deficient adenovirus carrying the CFTR gene (Ad.CFTR) to the airways. Results obtained in vitro and in Rhesus monkeys suggest that the delivery of recombinant adenovirus as an aerosol is feasible and is not associated with severe toxicity after single or double administration depending on the Ad.CFTR dose. This study supports the concept of aerosolization as a delivery method for adenovirus-mediated lung gene therapy.
Sené
C
C
Transgene S.A., Strasbourg, France.
Bout
A
A
Imler
J L
JL
Schultz
H
H
Willemot
J M
JM
Hennebel
V
V
Zurcher
C
C
Valerio
D
D
Lamy
D
D
Pavirani
A
A
D000256:Adenoviridae / Q000235:genetics*; D000336:Aerosols; D000818:Animals; D001483:Base Sequence; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D003673:Defective Viruses / Q000235:genetics; D005240:Feasibility Studies; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000821:virology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012137:Respiratory System / Q000821:virology
D000336:Aerosols; C505032:CFTR protein, human; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA