PMID- 26847924
OWN - NLM
STAT- MEDLINE
DCOM- 20170823
LR  - 20180212
IS  - 1557-7422 (Electronic)
IS  - 1043-0342 (Linking)
VI  - 27
IP  - 7
DP  - 2016 Jul
TI  - Sequential Adeno-Associated Viral Vector Serotype 9-Green Fluorescent Protein 
      Gene Transfer Causes Massive Inflammation and Intense Immune Response in Rat 
      Striatum.
PG  - 528-43
LID - 10.1089/hum.2015.083 [doi]
AB  - Green fluorescent protein (GFP) is a broadly used live cell reporter for gene 
      transduction although side effects associated with GFP in gene transfer are 
      reported. The present study was designed to systematically examine host 
      responses, including inflammatory and immune responses, induced by persistent 
      overexpression of the GFP gene mediated by adeno-associated viral vector serotype 
      9 (AAV9), and their effects on GFP gene transduction in rat striatum. Our results 
      show that host responses against AAV9-GFP transduction, and GFP transgene 
      expression in the striatum exhibited a temporal and dose-dependent pattern. Both 
      muscular and striatal delivery of AAV9-GFP increased levels of inflammation and 
      immune reactions against sequential AAV9-GFP transduction in the striatum, 
      leading to reduced levels of GFP expression. We also observed that rat sera from 
      sequential administrations of AAV9-GFP group had significantly higher levels of 
      neutralizing antibody against AAV9 vectors when compared with the age-matched 
      rats. As excessive GFP can trigger vigorous inflammation and intense immune 
      response after GFP gene transduction, the use of GFP as a live cell marker 
      protein should be deliberated, especially in repeated administration studies.
FAU - Yang, Chun
AU  - Yang C
AD  - 1 Department of Anatomy, Capital Medical University , Beijing, China .
FAU - Hao, Fei
AU  - Hao F
AD  - 1 Department of Anatomy, Capital Medical University , Beijing, China .
FAU - He, Jun
AU  - He J
AD  - 2 Department of Anatomy, Qiqihar Medical University , Qiqihar, Heilongjiang, 
      China .
FAU - Lu, Tao
AU  - Lu T
AD  - 1 Department of Anatomy, Capital Medical University , Beijing, China .
FAU - Klein, Ronald L
AU  - Klein RL
AD  - 3 Department of Pharmacology, Toxicology and Neuroscience, Louisiana State 
      University Health Sciences Center , Shreveport, Louisiana.
FAU - Zhao, Li-Ru
AU  - Zhao LR
AD  - 4 Department of Neurosurgery, Upstate Medical University , Syracuse, New York.
FAU - Duan, Wei-Ming
AU  - Duan WM
AD  - 1 Department of Anatomy, Capital Medical University , Beijing, China .
AD  - 5 Center of Parkinson's Disease, Beijing Institute for Brain Disorders , Beijing, 
      China .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160316
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Brain/*immunology/metabolism/pathology
MH  - Corpus Striatum/*immunology/metabolism/pathology
MH  - Dependovirus/*genetics
MH  - Female
MH  - Gene Transfer Techniques
MH  - Genetic Vectors/*administration & dosage
MH  - Green Fluorescent Proteins/*genetics/metabolism
MH  - Inflammation/*etiology/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serogroup
EDAT- 2016/02/06 06:00
MHDA- 2017/08/24 06:00
CRDT- 2016/02/06 06:00
PHST- 2016/02/06 06:00 [entrez]
PHST- 2016/02/06 06:00 [pubmed]
PHST- 2017/08/24 06:00 [medline]
AID - 10.1089/hum.2015.083 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2016 Jul;27(7):528-43. doi: 10.1089/hum.2015.083. Epub 2016 Mar 
      16.