PMID- 18044793
OWN - NLM
STAT- MEDLINE
DCOM- 20080328
LR  - 20071224
IS  - 1099-498X (Print)
IS  - 1099-498X (Linking)
VI  - 10
IP  - 1
DP  - 2008 Jan
TI  - AAV serotype 1 mediates more efficient gene transfer to pig myocardium than AAV 
      serotype 2 and plasmid.
PG  - 33-41
AB  - Adeno-associated virus (AAV) has many properties of an ideal vector for delivery 
      of therapeutic genes into the myocardium. Previous studies in a mouse model of 
      myocardial infarction showed that AAV serotype 1 (AAV1) is superior to AAV 
      serotypes 2-5 to transfer genes into the myocardium by direct injection. Since 
      vectors may behave differently in humans and because the human and the pig hearts 
      resemble each other closely, we tested whether AAV1 is also superior to AAV2 in 
      transferring genes into the pig myocardium. We also compared gene transduction 
      efficiency between AAV vectors and plasmid. We injected CMVLacZ and CMVVEGF 
      (vectors with the cytomegalovirus (CMV) promoter driving LacZ and VEGF gene 
      expression) unpackaged or packaged in AAV serotypes 1 or 2 capsids into pig 
      myocardium. Hearts were collected 3, 14 and 28 days after the injection. Gene 
      expression was analyzed by real-time reverse-transcription polymerase chain 
      reaction (RT-PCR) and histological staining. Capillaries and smooth muscle 
      alpha-actin (SMA)-positive vessels were quantified. Potential lymphocyte 
      infiltration at the injection sites was analyzed by immunostaining using specific 
      antibodies. As in the mouse, AAV1 mediated better gene transduction than AAV2. 
      Plasmid mediated minimal gene expression only. More capillaries and SMA-positive 
      vessels were detected at AAV1CMVVEGF- and AAV2CMVVEGF-injected than 
      AAV1CMVLacZ-injected sites. We did not detect inflammatory cell infiltration at 
      the injection sites. In conclusion, by direct injection, AAV1 is more efficient 
      than AAV2, and plasmid is inefficient in mediating gene transfer into the pig 
      myocardium. AAV-mediated VEGF gene transfer can also induce neovascular formation 
      in the pig myocardium.
CI  - (c) 2007 John Wiley & Sons, Ltd.
FAU - Su, H
AU  - Su H
AD  - Cardiovascular Research Institute, University of California, San Francisco, San 
      Francisco, CA 94143-0793, USA. hua.su@ucsf.edu
FAU - Yeghiazarians, Y
AU  - Yeghiazarians Y
FAU - Lee, A
AU  - Lee A
FAU - Huang, Y
AU  - Huang Y
FAU - Arakawa-Hoyt, J
AU  - Arakawa-Hoyt J
FAU - Ye, J
AU  - Ye J
FAU - Orcino, G
AU  - Orcino G
FAU - Grossman, W
AU  - Grossman W
FAU - Kan, Y W
AU  - Kan YW
LA  - eng
GR  - HL67969/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Animals
MH  - Blood Vessels/cytology
MH  - Cell Line
MH  - Dependovirus/*classification/*metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - *Gene Transfer Techniques
MH  - Humans
MH  - Immunohistochemistry
MH  - Injections
MH  - Myocardium/cytology/*metabolism
MH  - Plasmids/*metabolism
MH  - RNA, Messenger
MH  - Serotyping
MH  - Swine
MH  - Vascular Endothelial Growth Factor A/genetics
MH  - beta-Galactosidase/genetics
EDAT- 2007/11/30 09:00
MHDA- 2008/03/29 09:00
CRDT- 2007/11/30 09:00
PHST- 2007/11/30 09:00 [pubmed]
PHST- 2008/03/29 09:00 [medline]
PHST- 2007/11/30 09:00 [entrez]
AID - 10.1002/jgm.1129 [doi]
PST - ppublish
SO  - J Gene Med. 2008 Jan;10(1):33-41. doi: 10.1002/jgm.1129.