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学科主题: 基础医学
题名:
MicroRNA-regulated, Systemically Delivered rAAV9: A Step Closer to CNS-restricted Transgene Expression
作者: Xie, Jun1,2; Xie, Qing1,3; Zhang, Hongwei1,2; Ameres, Stefan L.4; Hung, Jui-Hung5; Su, Qin1; He, Ran1; Mu, Xin1,6; Ahmed, Seemin Seher1,2; Park, Soyeon1,2; Kato, Hiroki7; Li, Chengjian4; Mueller, Christian1,8; Mello, Craig C.7,9; Weng, Zhiping10; Flotte, Terence R.1,2,8; Zamore, Phillip D.4,9; Gao, Guangping1,2
刊名: MOLECULAR THERAPY
发表日期: 2011-03-01
DOI: 10.1038/mt.2010.279
卷: 19, 期:3, 页:526-535
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]: AMYOTROPHIC-LATERAL-SCLEROSIS ; GENE-THERAPY ; PARKINSONS-DISEASE ; MOTOR-NEURONS ; AAV VECTOR ; IN-VIVO ; PHASE-I ; RECOGNITION ; EVOLUTION ; TROPISM
英文摘要:

Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain-barrier and achieve efficient and stable transvascular gene transfer to the central nervous system (CNS) hold significant promise for treating CNS disorders. However, following intravascular delivery, these vectors also target liver, heart, skeletal muscle, and other tissues, which may cause untoward effects. To circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to repress rAAV expression outside the CNS, by engineering perfectly complementary miRNA-binding sites into the rAAV9 genome. This approach allowed simultaneous multi-tissue regulation and CNS-directed stable transgene expression without detectably perturbing the endogenous miRNA pathway. Regulation of rAAV expression by miRNA was primarily via site-specific cleavage of the transgene mRNA, generating specific 5′ and 3′ mRNA fragments. Our findings promise to facilitate the development of miRNA-regulated rAAV for CNS-targeted gene delivery and other applications.

语种: 英语
所属项目编号: DK 58327 ; 5P30DK 32520
项目资助者: University of Massachusetts Medical School ; National Institute of Health ; National Institute of Diabetes and Digestive and Kidney Diseases
WOS记录号: WOS:000287911600012
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52871
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA
2.Univ Massachusetts, Sch Med, Gene Therapy Ctr, Worcester, MA 01655 USA
3.Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA
4.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100871, Peoples R China
5.Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01655 USA
6.Xi An Jiao Tong Univ, Dept Dermatol, Affiliated Hosp 1, Coll Med, Xian 710049, Shanxi, Peoples R China
7.Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01655 USA
8.Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01655 USA
9.Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01655 USA
10.Univ Massachusetts, Sch Med, Program Bioinformat, Worcester, MA 01655 USA

Recommended Citation:
Xie, Jun,Xie, Qing,Zhang, Hongwei,et al. MicroRNA-regulated, Systemically Delivered rAAV9: A Step Closer to CNS-restricted Transgene Expression[J]. MOLECULAR THERAPY,2011,19(3):526-535.
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