PMID- 16180126
OWN - NLM
STAT- MEDLINE
DCOM- 20051214
LR  - 20181113
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 22
IP  - 10
DP  - 2005 Oct
TI  - In vivo human MCP-1 transfection in porcine arteries by intravascular 
      electroporation.
PG  - 1685-91
AB  - PURPOSE: The purpose of this study was to develop a nonviral gene transfer method 
      for therapeutic delivery of the human monocyte chemoattractant protein-1 (MCP-1) 
      in patients with peripheral artery disease, using local catheter-mediated 
      electrotransfer of naked plasmid DNA into arteries. METHODS: Arterial walls of 
      the A. profunda femoris of pigs were transfected either with a human MCP-1 or 
      with a firefly luciferase-encoding DNA construct. The efficacy of electrotransfer 
      of DNA was analyzed after 2 days by quantitative polymerase chain reaction (PCR) 
      or luciferase activity measurements. To optimize MCP-1 gene transfer conditions, 
      a voltage range of 60-150 V was applied as a train of six square pulses of 20 ms 
      each at 1 Hz and was combined with a dose of 150 microg DNA. Subsequently, the 
      optimized voltage was used to test a dose range of 80-300 microg DNA. RESULTS: 
      The voltage optimum for arterial transfection was observed at 80 volts. Using 
      this setting, the dose application of 300 microg MCP-1 plasmid DNA (the maximal 
      dose tested) demonstrated the highest MCP-1 expression signal. The electric 
      pulses and the transfer and expression of human MCP-1 per se did not induce 
      endogenous porcine MCP-1 expression in treated arteries. Interestingly, 
      angioplastic predilation of the artery before gene transfer, which had originally 
      been postulated to enhance transfection by improving access of the plasmid to 
      subendothelial cell layers, resulted in an attenuated transfection efficacy. 
      CONCLUSIONS: The present study demonstrates that transluminal catheter-based 
      electroporation provides an efficient technology for nonviral intravascular gene 
      transfer by just applying unformulated DNA.
FAU - Seidler, Randolph W
AU  - Seidler RW
AD  - Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, 06877, USA.
FAU - Allgauer, Susanne
AU  - Allgauer S
FAU - Ailinger, Susanne
AU  - Ailinger S
FAU - Sterner, Andreas
AU  - Sterner A
FAU - Dev, Nagendu
AU  - Dev N
FAU - Rabussay, Dietmar
AU  - Rabussay D
FAU - Doods, Henri
AU  - Doods H
FAU - Lenter, Martin C
AU  - Lenter MC
LA  - eng
PT  - Journal Article
DEP - 20050922
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Chemokine CCL2)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Carotid Arteries/*drug effects
MH  - Catheterization/instrumentation/*methods
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Electroporation/*methods
MH  - Humans
MH  - Luciferases/genetics/metabolism
MH  - Swine
MH  - Transfection/instrumentation/*methods
EDAT- 2005/09/24 09:00
MHDA- 2005/12/15 09:00
CRDT- 2005/09/24 09:00
PHST- 2005/03/09 00:00 [received]
PHST- 2005/06/06 00:00 [accepted]
PHST- 2005/09/24 09:00 [pubmed]
PHST- 2005/12/15 09:00 [medline]
PHST- 2005/09/24 09:00 [entrez]
AID - 10.1007/s11095-005-6334-9 [doi]
PST - ppublish
SO  - Pharm Res. 2005 Oct;22(10):1685-91. doi: 10.1007/s11095-005-6334-9. Epub 2005 Sep 
      22.