PMID- 16791284
OWN - NLM
STAT- MEDLINE
DCOM- 20070521
LR  - 20131121
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 13
IP  - 23
DP  - 2006 Dec
TI  - Intravenously administered oligonucleotides can be delivered to conducting airway 
      epithelium via the bronchial circulation.
PG  - 1628-38
AB  - Topical gene transfer to the airways of cystic fibrosis (CF) patients has been 
      inefficient, partly due to extracellular barriers such as sputum. In an attempt 
      to circumvent these, we assessed whether airway epithelial cells can be 
      transfected by intravenous (i.v.) administration of liposome-complexed or "naked" 
      oligonucleotides (ODNs). The conducting airways are the likely target for CF 
      therapy and are supplied by the bronchial circulation. Consequently, we assessed 
      ODN transfer in the mouse trachea and main bronchi as these are supplied by the 
      bronchial circulation. Liposome-protamine-DNA (LPD) complexes were detected in 
      the bronchial circulation but did not transfect conducting airway epithelial 
      cells, even in the presence of microvascular leakage. In contrast, 'naked' ODNs 
      were delivered to 17% (inter-quartile range (IQR) 10-34%) and 35% (IQR 24-59%) of 
      epithelial cells when injected at 500 microg/animal, without and with 
      microvascular leakage, respectively. Two types of nuclear signal were observed; 
      punctate in cells throughout the airways (3%, IQR 2-6%, and 6%, IQR 4-7%, of 
      cells when delivered without and with microvascular leakage, respectively) and 
      diffuse in a small number of epithelial cells in the proximal trachea. ODNs may 
      be relevant to CF in a variety of ways and these data suggest one way towards 
      implementing their use.
FAU - Holder, E
AU  - Holder E
AD  - Department of Gene Therapy, Faculty of Medicine, Imperial College, Manrisa Road, 
      London, UK.
FAU - Griesenbach, U
AU  - Griesenbach U
FAU - Li, S
AU  - Li S
FAU - Huang, L
AU  - Huang L
FAU - Rogers, D F
AU  - Rogers DF
FAU - Jeffery, P K
AU  - Jeffery PK
FAU - Geddes, D M
AU  - Geddes DM
FAU - Alton, E W F W
AU  - Alton EW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060622
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Liposomes)
RN  - 0 (NF-kappa B)
RN  - 0 (Oligonucleotides)
RN  - 0 (Platelet Activating Factor)
RN  - 820484N8I3 (Histamine)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Bradykinin/pharmacology
MH  - Bronchi/*blood supply
MH  - Cell Nucleus/metabolism
MH  - Cystic Fibrosis/metabolism/therapy
MH  - Cytoplasm/metabolism
MH  - Epithelial Cells/metabolism
MH  - Extravasation of Diagnostic and Therapeutic Materials
MH  - Gene Expression
MH  - Genetic Therapy/*methods
MH  - Histamine/pharmacology
MH  - Injections, Intravenous
MH  - Liposomes
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microcirculation
MH  - Microscopy, Fluorescence
MH  - NF-kappa B/genetics
MH  - Oligonucleotides/*administration & dosage
MH  - Platelet Activating Factor/pharmacology
MH  - Respiratory Mucosa/*metabolism
MH  - Transfection/*methods
EDAT- 2006/06/23 09:00
MHDA- 2007/05/22 09:00
CRDT- 2006/06/23 09:00
PHST- 2006/06/23 09:00 [pubmed]
PHST- 2007/05/22 09:00 [medline]
PHST- 2006/06/23 09:00 [entrez]
AID - 3302811 [pii]
AID - 10.1038/sj.gt.3302811 [doi]
PST - ppublish
SO  - Gene Ther. 2006 Dec;13(23):1628-38. doi: 10.1038/sj.gt.3302811. Epub 2006 Jun 22.