PMID- 25915925
OWN - NLM
STAT- MEDLINE
DCOM- 20160418
LR  - 20181203
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 23
IP  - 7
DP  - 2015 Jul
TI  - Cardiac AAV9 Gene Delivery Strategies in Adult Canines: Assessment by Long-term 
      Serial SPECT Imaging of Sodium Iodide Symporter Expression.
PG  - 1211-1221
LID - S1525-0016(16)30152-6 [pii]
LID - 10.1038/mt.2015.78 [doi]
AB  - Heart failure is a leading cause of morbidity and mortality, and cardiac gene 
      delivery has the potential to provide novel therapeutic approaches. 
      Adeno-associated virus serotype 9 (AAV9) transduces the rodent heart efficiently, 
      but cardiotropism, immune tolerance, and optimal delivery strategies in large 
      animals are unclear. In this study, an AAV9 vector encoding canine sodium iodide 
      symporter (NIS) was administered to adult immunocompetent dogs via epicardial 
      injection, coronary infusion without and with cardiac recirculation, or 
      endocardial injection via a novel catheter with curved needle and both end- and 
      side-holes. As NIS mediates cellular uptake of clinical radioisotopes, expression 
      was tracked by single-photon emission computerized tomography (SPECT) imaging in 
      addition to Western blot and immunohistochemistry. Direct epicardial or 
      endocardial injection resulted in strong cardiac expression, whereas expression 
      after intracoronary infusion or cardiac recirculation was undetectable. A 
      threshold myocardial injection dose that provides robust nonimmunogenic 
      expression was identified. The extent of transmural myocardial expression was 
      greater with the novel catheter versus straight end-hole needle delivery. 
      Furthermore, the authors demonstrate that cardiac NIS reporter gene expression 
      and duration can be quantified using serial noninvasive SPECT imaging up to 1 
      year after vector administration. These data are relevant to efforts to develop 
      cardiac gene delivery as heart failure therapy.
FAU - Moulay, Gilles
AU  - Moulay G
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Ohtani, Tomohito
AU  - Ohtani T
AD  - Osaka University, Osaka, Japan.
FAU - Ogut, Ozgur
AU  - Ogut O
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Guenzel, Adam
AU  - Guenzel A
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Behfar, Atta
AU  - Behfar A
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Zakeri, Rosita
AU  - Zakeri R
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Haines, Philip
AU  - Haines P
AD  - University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Storlie, Jimmy
AU  - Storlie J
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Bowen, Lorna
AU  - Bowen L
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Pham, Linh
AU  - Pham L
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Kaye, David
AU  - Kaye D
AD  - Baker Heart Research Institute, Melbourne, Australia.
FAU - Sandhu, Gurpreet
AU  - Sandhu G
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - O'Connor, Michael
AU  - O'Connor M
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Russell, Stephen
AU  - Russell S
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Redfield, Margaret
AU  - Redfield M
AD  - Mayo Clinic, Rochester, Minnesota, USA. Electronic address: 
      redfield.margaret@mayo.edu.
LA  - eng
GR  - P01 HL076611/HL/NHLBI NIH HHS/United States
GR  - R01 HL105418/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150427
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Symporters)
RN  - 4XE5NDT4K1 (sodium-iodide symporter)
SB  - IM
MH  - Animals
MH  - Dependovirus/genetics
MH  - Dogs
MH  - Gene Expression
MH  - *Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - Genetic Vectors
MH  - Heart Failure/genetics/pathology/*therapy
MH  - Humans
MH  - Myocardium/metabolism
MH  - Pericardium/pathology
MH  - Symporters/administration & dosage/*genetics
MH  - Tomography, Emission-Computed, Single-Photon
PMC - PMC4817780
EDAT- 2015/04/29 06:00
MHDA- 2016/04/19 06:00
PMCR- 2016/07/01
CRDT- 2015/04/28 06:00
PHST- 2014/11/19 00:00 [received]
PHST- 2015/04/18 00:00 [accepted]
PHST- 2015/04/28 06:00 [entrez]
PHST- 2015/04/29 06:00 [pubmed]
PHST- 2016/04/19 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - S1525-0016(16)30152-6 [pii]
AID - 10.1038/mt.2015.78 [doi]
PST - ppublish
SO  - Mol Ther. 2015 Jul;23(7):1211-1221. doi: 10.1038/mt.2015.78. Epub 2015 Apr 27.