title: Recombinant adeno-associated virus serotype 9 in a mouse model of atherosclerosis: Determination of the optimal expression time in vivo.
abstract: Adeno-associated virus 9 (AAV9) has been identified as one of the optimal gene transduction carriers for gene therapy. The aim of the present study was to determine the gene transfection efficiency and safety of an AAV9 vector produced using a recombinant baculovirus (rBac)‑based system. AAV9‑cytomegalovirus (CMV)-green fluorescent protein was produced using an rBac system and the resulting vector particles were injected intravenously into mice. Animals were sacrificed at 14, 21, 28, 35, 60, 90 and 120 days following injection. GFP expression in aortic vasculature and aortic plaques in C57/6B and apolipoprotein E‑/‑ mice was analyzed by fluorescence imaging and western blotting. In vivo analyses of biological markers of liver and heart damage, and renal function, as well as in vitro terminal deoxynucleotidyl transferase dUTP nick end labeling analysis were used to determine the toxicity of the AAV9 carrier. The findings of the present study demonstrated that AAV9 viral vectors packaged using the rBac system functioned appropriately in arteriosclerosis plaques. The CMV promoter significantly induced GFP expression in the vascular plaque in a time-dependent manner. AAV9‑CMV viral particles did not lead to heart, liver or renal damage and no change in apoptotic rate was identified. These findings indicated that AAV9-CMV may be effectively and safely used to transfect genes into atherosclerotic plaques.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhai
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Bangdang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Lai
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016367:Baculoviridae / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000032:analysis / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011401:Promoter Regions, Genetic; D014161:Transduction, Genetic; D014162:Transfection / Q000379:methods*
chemical_list: D049452:Green Fluorescent Proteins