title: Sequential Adeno-Associated Viral Vector Serotype 9-Green Fluorescent Protein Gene Transfer Causes Massive Inflammation and Intense Immune Response in Rat Striatum.
abstract: 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.
authors: 1 Department of Anatomy, Capital Medical University , Beijing, China .
authors: Chun
authors: C
authors: Yang
authors: 1 Department of Anatomy, Capital Medical University , Beijing, China .
authors: Fei
authors: F
authors: Hao
authors: 2 Department of Anatomy, Qiqihar Medical University , Qiqihar, Heilongjiang, China .
authors: Jun
authors: J
authors: He
authors: 1 Department of Anatomy, Capital Medical University , Beijing, China .
authors: Tao
authors: T
authors: Lu
authors: 3 Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center , Shreveport, Louisiana.
authors: Ronald L
authors: RL
authors: Klein
authors: 4 Department of Neurosurgery, Upstate Medical University , Syracuse, New York.
authors: Li-Ru
authors: LR
authors: Zhao
authors: 1 Department of Anatomy, Capital Medical University , Beijing, China .|5 Center of Parkinson's Disease, Beijing Institute for Brain Disorders , Beijing, China .
authors: Wei-Ming
authors: WM
authors: Duan
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins / Q000235:genetics* / Q000378:metabolism; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D065288:Serogroup
chemical_list: D049452:Green Fluorescent Proteins