Enhanced in Vivo Blood-Brain Barrier Penetration by Circular Tau-Transferrin Receptor Bifunctional Aptamer for Tauopathy Therapy

doi:10.1021/jacs.9b11490

	Enhanced in Vivo Blood-Brain Barrier Penetration by Circular Tau-Transferrin Receptor Bifunctional Aptamer for Tauopathy Therapy
	Li, Xiaowei 3,4,5; Yang, Yu 3,4,5; Zhao, Hengzhi 3,4,5; Zhu, Tian 1; Yang, Zhihui 1; Xu, Haiyan 1; Fu, Yueqiang 1; Lin, Fan 1; Pan, Xiaoshu 3,4,5; Li, Long 3,4,5
刊名	JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
	2020-02-26
卷号	142
ISSN号	0002-7863
DOI	10.1021/jacs.9b11490
通讯作者	Wang, Kevin K.(kwang@ufl.edu) ; Tan, Weihong(tan@hnu.edu.cn)
英文摘要	The lack of blood-brain barrier (BBB) penetrating ability has hindered the delivery of many therapeutic agents for tauopathy treatment. In this study, we report the synthesis of a circular bifunctional aptamer to enhance the in vivo BBB penetration for better tauopathy therapy. The circular aptamer consists of one reported transferrin receptor (TfR) aptamer to facilitate TfR-aptamer recognition-induced transcytosis across BBB endothelial cells, and one Tau protein aptamer that we recently selected to inhibit Tau phosphorylation and other tauopathy-related pathological events in the brain. This novel circular Tau-TfR bifunctional aptamer displays significantly improved plasma stability and brain exposure, as well as the ability to disrupt tauopathy and improve traumatic brain injury (TBI)-induced cognitive/memory deficits in vivo, providing important proof-of-principle evidence that circular Tau-TfR aptamer can be further developed into diagnostic and therapeutic candidates for tauopathies.
资助项目	DOD[AZ180105] ; DOD[21827811]
WOS关键词	PROTEIN ; AGGREGATION ; ANTIBODIES ; VITRO ; MODEL
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000517360400024
资助机构	DOD
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103907]
专题	中国科学院合肥物质科学研究院
通讯作者	Wang, Kevin K.; Tan, Weihong
作者单位	1.Univ Florida, McKnight Brain Inst, Dept Psychiat, Dept Emergency Med,Dept Neurosci, Gainesville, FL 32611 USA 2.Malcom Randall Vet Affairs Med Ctr, BRRC, Gainesville, FL 32608 USA 3.Univ Florida, UF Genet Inst, Hlth Canc Ctr, Ctr Res Bio Nano Interface,Dept Chem, Gainesville, FL 32611 USA 4.Univ Florida, UF Genet Inst, Hlth Canc Ctr, Ctr Res Bio Nano Interface,Dept Physiol & Funct G, Gainesville, FL 32611 USA 5.Univ Florida, McKnight Brain Inst, Gainesville, FL 32611 USA 6.Hunan Univ, Aaptamer Engn Ctr Hunan Prov, Coll Biol,Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr,Mol Sc, Changsha 410082, Hunan, Peoples R China 7.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou 310022, Zhejiang, Peoples R China 8.Univ Chinese Acad Sci, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China 9.Liaocheng Univ, Sch Chem & Chem Engn, Liaocheng 252059, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Li, Xiaowei,Yang, Yu,Zhao, Hengzhi,et al. Enhanced in Vivo Blood-Brain Barrier Penetration by Circular Tau-Transferrin Receptor Bifunctional Aptamer for Tauopathy Therapy[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2020,142.
APA	Li, Xiaowei.,Yang, Yu.,Zhao, Hengzhi.,Zhu, Tian.,Yang, Zhihui.,...&Tan, Weihong.(2020).Enhanced in Vivo Blood-Brain Barrier Penetration by Circular Tau-Transferrin Receptor Bifunctional Aptamer for Tauopathy Therapy.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,142.
MLA	Li, Xiaowei,et al."Enhanced in Vivo Blood-Brain Barrier Penetration by Circular Tau-Transferrin Receptor Bifunctional Aptamer for Tauopathy Therapy".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 142(2020).