Direct gene transfer of human CFTR into human bronchial epithelia of xenografts with E1-deleted adenoviruses.
We describe the use of a human bronchial xenograft model for studying the efficiency and biology of in vivo gene transfer into human bronchial epithelia with recombinant E1 deleted adenoviruses. All cell types in the surface epithelium except basal cells efficiently expressed the adenoviral transduced recombinant genes, lacZ and CFTR, for 3-5 weeks. Stable transgene expression was associated with high level expression of the early adenoviral gene, E2a, in a subset of transgene expressing cells and virtually undetectable expression of the late adenoviral genes encoding the structural proteins, hexon and fiber. These studies begin to address important issues that relate to safety and in vivo efficacy of recombinant adenoviruses for gene delivery into the human airway.
Engelhardt
J F
JF
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0650.
Yang
Y
Y
Stratford-Perricaudet
L D
LD
Allen
E D
ED
Kozarsky
K
K
Perricaudet
M
M
Yankaskas
J R
JR
Wilson
J M
JM
D017500:Adenovirus E1A Proteins / Q000172:deficiency / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics* / Q000302:isolation & purification; D000818:Animals; D001980:Bronchi / Q000378:metabolism / Q000382:microbiology / Q000637:transplantation*; D002454:Cell Differentiation; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D003673:Defective Viruses / Q000235:genetics* / Q000302:isolation & purification; D004848:Epithelium / Q000378:metabolism / Q000382:microbiology / Q000637:transplantation; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007866:Leg; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012449:Safety; D014132:Trachea / Q000637:transplantation; D014162:Transfection; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
D017500:Adenovirus E1A Proteins; C505032:CFTR protein, human; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator