PMID- 11485630
OWN - NLM
STAT- MEDLINE
DCOM- 20011205
LR  - 20060421
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 12
IP  - 11
DP  - 2001 Jul 20
TI  - Aerosol and lobar administration of a recombinant adenovirus to individuals with 
      cystic fibrosis. II. Transfection efficiency in airway epithelium.
PG  - 1383-94
AB  - A phase I clinical trial was conducted in which recombinant adenovirus containing 
      the cystic fibrosis trans-membrane regulator (CFTR) (Ad2/CFTR) was administered 
      by bronchoscopic instillation or aerosolization to the lungs of cystic fibrosis 
      (CF) patients. In this paper, we evaluate the efficiency of Ad2/CFTR-mediated 
      transduction of bronchial airway cells. The ability of an Ad2/CFTR vector to 
      transduce airway cells was first evaluated in patients to whom the vector was 
      administered by bronchoscopic instillation. Cells at the administration site were 
      collected 2 days after treatment by bronchoscopic brushing. Ad2-specific CFTR DNA 
      was detected in four of five individuals by PCR, and Ad2-specific CFTR RNA was 
      detected in three of five individuals by RT-PCR. Ad2/CFTR-mediated transduction 
      of airway epithelial cells was then determined in CF individuals receiving this 
      vector by aerosol inhalation. Ad2-specific CFTR DNA was detected in 13 of 13 
      individuals 2 days after aerosolization, and in 3 of 5 individuals 7 days after 
      aerosolization. Ad2-specific RNA was detected in 4 of 13 individuals on day 2, 
      but was not detected in the 5 individuals tested on day 7. The percentage of 
      airway epithelial cells containing nuclear-localized vector DNA was < or =2.4% as 
      determined by fluorescence in situ hybridization (FISH). However, in some cases, 
      a high percentage of nonepithelial mononuclear cells or squamous metaplastic 
      epithelial cells was infected with the adenoviral vector. In conclusion, aerosol 
      administration is a feasible means to distribute adenoviral vectors throughout 
      the conducting airways, but improvements in adenovirus-mediated transduction of 
      airway epithelial cells are necessary before gene therapy for CF will be 
      effective.
FAU - Perricone, M A
AU  - Perricone MA
AD  - Genzyme Corporation, Framingham, MA 01701, USA. michael. perricone@genyme.com
FAU - Morris, J E
AU  - Morris JE
FAU - Pavelka, K
AU  - Pavelka K
FAU - Plog, M S
AU  - Plog MS
FAU - O'Sullivan, B P
AU  - O'Sullivan BP
FAU - Joseph, P M
AU  - Joseph PM
FAU - Dorkin, H
AU  - Dorkin H
FAU - Lapey, A
AU  - Lapey A
FAU - Balfour, R
AU  - Balfour R
FAU - Meeker, D P
AU  - Meeker DP
FAU - Smith, A E
AU  - Smith AE
FAU - Wadsworth, S C
AU  - Wadsworth SC
FAU - St George, J A
AU  - St George JA
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (CFTR protein, human)
RN  - 0 (DNA, Recombinant)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Administration, Inhalation
MH  - Adolescent
MH  - Adult
MH  - Bronchoscopy
MH  - Cystic Fibrosis/*therapy
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/*genetics
MH  - DNA, Recombinant
MH  - Female
MH  - Genetic Vectors
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Instillation, Drug
MH  - Male
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins/isolation & purification
MH  - Respiratory Mucosa/*metabolism
MH  - Time Factors
MH  - Transduction, Genetic
MH  - *Transfection
EDAT- 2001/08/04 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/08/04 10:00
PHST- 2001/08/04 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/08/04 10:00 [entrez]
AID - 10.1089/104303401750298544 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2001 Jul 20;12(11):1383-94. doi: 10.1089/104303401750298544.