{"doi":"10.1021/jacs.9b11490","title":"Enhanced in Vivo Blood–Brain Barrier Penetration by Circular Tau–Transferrin Receptor Bifunctional Aptamer for Tauopathy Therapy","abstract":"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.","journal":"Journal of the American Chemical Society","year":2020,"id":52889,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":125,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9472,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":268369,"name":"Yu Yang","orcid":"0000-0002-4518-3299","position":1,"is_corresponding":false},{"id":268370,"name":"Hengzhi Zhao","orcid":"0000-0002-5913-8106","position":2,"is_corresponding":false},{"id":269548,"name":"Tian Zhu","orcid":null,"position":3,"is_corresponding":false},{"id":268371,"name":"Zhihui Yang","orcid":"0000-0002-9289-013X","position":4,"is_corresponding":false},{"id":268372,"name":"Haiyan Xu","orcid":"0000-0003-3068-4370","position":5,"is_corresponding":false},{"id":268373,"name":"Yueqiang Fu","orcid":"0009-0003-8840-1879","position":6,"is_corresponding":false},{"id":268374,"name":"Fan Lin","orcid":"0000-0002-9435-5181","position":7,"is_corresponding":false},{"id":268375,"name":"Xiaoshu Pan","orcid":"0000-0003-1896-2198","position":8,"is_corresponding":false},{"id":268376,"name":"Long Li","orcid":"0000-0001-9535-8977","position":9,"is_corresponding":false},{"id":268377,"name":"Cheng Cui","orcid":"0000-0001-8402-6459","position":10,"is_corresponding":false},{"id":268378,"name":"Min Hong","orcid":"0009-0007-0048-5748","position":11,"is_corresponding":false},{"id":268379,"name":"Lu Yang","orcid":"0000-0001-6049-6763","position":12,"is_corresponding":false},{"id":4449,"name":"Kevin Wang","orcid":"0000-0002-9343-6473","position":13,"is_corresponding":false},{"id":88885,"name":"Weihong Tan","orcid":"0000-0002-8066-1524","position":14,"is_corresponding":false},{"id":259692,"name":"Xiaowei Li","orcid":"0000-0003-0714-1140","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T20:43:25.742124Z","pmid":"31991082","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}