PMID- 28322993
OWN - NLM
STAT- MEDLINE
DCOM- 20170608
LR  - 20181113
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Print)
IS  - 0378-1119 (Linking)
VI  - 618
DP  - 2017 Jun 30
TI  - Intra-luminal gene therapy in the porcine artery using a recombinant 
      adeno-associated virus 9.
PG  - 24-27
LID - S0378-1119(17)30177-4 [pii]
LID - 10.1016/j.gene.2017.03.019 [doi]
AB  - The ability to improve or restore blood flow and promote healing in ischemic 
      tissue has many potential clinical applications. Augmentation by direct delivery 
      of growth factors may further enhance results, but requires a method for 
      sustained delivery. In this study, we have tested the ability of adeno-associated 
      virus 9 (AAV9) delivered within the lumen of a porcine artery to transfect the 
      vessel and produce a desired product. The marker chosen was green fluorescent 
      protein (GFP) (Ke et al., 2011). In 4 farm pigs the cranial tibial artery was 
      surgically exposed. The vessel was temporarily clamped proximally, and divided 
      distally. A cannula was placed intraluminally, and the arterial segment was 
      injected with 1x10E13 particles of AAV9.CB7.CI.GFP.WPRE.rBG. At 14days the 
      transfected cranial tibial artery as well as the liver, spleen and kidneys were 
      harvested. ELISA and reverse transcriptase quantitative polymerase chain reaction 
      (RT-qPCR) were used to analyze the artery for GFP production. Significant GFP 
      expression was seen in all transfected cranial tibial vessels, as determined by 
      both GFP protein production (ELISA) and mRNA (RT-qPCR). No GFP was identified in 
      liver, spleen or kidney, nor in the no-GFP control animal artery. 
      Adeno-associated virus 9 is an appropriate vector for gene therapy experiments in 
      the porcine artery model. This vector, and the intraluminal deliver method 
      described result in robust gene expression at 2weeks without evident systemic 
      spill of the virus. The ability to limit delivery of the gene to an isolated 
      segment of vessel is desirable for future research applications.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Rezaie, E S
AU  - Rezaie ES
AD  - Mayo Clinic, Department of Orthopedic Surgery, 200 1st St. SW, Rochester, MN 
      55905, United States. Electronic address: rezaie.elisa@mayo.edu.
FAU - Visser, N J
AU  - Visser NJ
AD  - Mayo Clinic, Department of Orthopedic Surgery, 200 1st St. SW, Rochester, MN 
      55905, United States.
FAU - Friedrich, P F
AU  - Friedrich PF
AD  - Mayo Clinic, Department of Orthopedic Surgery, 200 1st St. SW, Rochester, MN 
      55905, United States.
FAU - Shin, A Y
AU  - Shin AY
AD  - Mayo Clinic, Department of Orthopedic Surgery, 200 1st St. SW, Rochester, MN 
      55905, United States.
FAU - Bishop, A T
AU  - Bishop AT
AD  - Mayo Clinic, Department of Orthopedic Surgery, 200 1st St. SW, Rochester, MN 
      55905, United States.
LA  - eng
GR  - R01 AR049718/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20170318
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (DNA, Recombinant)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - DNA, Recombinant/administration & dosage/genetics
MH  - Dependovirus/*genetics
MH  - Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/administration & dosage/genetics
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Injections, Intra-Arterial
MH  - Swine
MH  - *Tibial Arteries
PMC - PMC5515074
MID - NIHMS865807
OTO - NOTNLM
OT  - Adeno associated virus
OT  - Gene therapy
OT  - Porcine
OT  - Vascular disease
EDAT- 2017/03/23 06:00
MHDA- 2017/06/09 06:00
PMCR- 2018/06/30
CRDT- 2017/03/22 06:00
PHST- 2017/01/21 00:00 [received]
PHST- 2017/02/22 00:00 [revised]
PHST- 2017/03/16 00:00 [accepted]
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2017/06/09 06:00 [medline]
PHST- 2017/03/22 06:00 [entrez]
PHST- 2018/06/30 00:00 [pmc-release]
AID - S0378-1119(17)30177-4 [pii]
AID - 10.1016/j.gene.2017.03.019 [doi]
PST - ppublish
SO  - Gene. 2017 Jun 30;618:24-27. doi: 10.1016/j.gene.2017.03.019. Epub 2017 Mar 18.