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dc.contributor.authorZhou, Y
dc.contributor.authorZhu, F
dc.contributor.authorLiu, Y
dc.contributor.authorZheng, M
dc.contributor.authorWang, Y
dc.contributor.authorZhang, D
dc.contributor.authorAnraku, Y
dc.contributor.authorZou, Y
dc.contributor.authorLi, J
dc.contributor.authorWu, H
dc.contributor.authorPang, X
dc.contributor.authorTao, W
dc.contributor.authorShimoni, O
dc.contributor.authorBush, A
dc.contributor.authorXue, X
dc.contributor.authorShi, B
dc.date.accessioned2020-11-17T04:03:20Z
dc.date.available2020-11-17T04:03:20Z
dc.date.issued2020-10-01
dc.identifierpii: 6/41/eabc7031
dc.identifier.citationZhou, Y., Zhu, F., Liu, Y., Zheng, M., Wang, Y., Zhang, D., Anraku, Y., Zou, Y., Li, J., Wu, H., Pang, X., Tao, W., Shimoni, O., Bush, A., Xue, X. & Shi, B. (2020). Blood-brain barrier-penetrating siRNA nanomedicine for Alzheimer's disease therapy. SCIENCE ADVANCES, 6 (41), https://doi.org/10.1126/sciadv.abc7031.
dc.identifier.issn2375-2548
dc.identifier.urihttp://hdl.handle.net/11343/251684
dc.description.abstractToxic aggregated amyloid-β accumulation is a key pathogenic event in Alzheimer's disease (AD), which derives from amyloid precursor protein (APP) through sequential cleavage by BACE1 (β-site APP cleavage enzyme 1) and γ-secretase. Small interfering RNAs (siRNAs) show great promise for AD therapy by specific silencing of BACE1. However, lack of effective siRNA brain delivery approaches limits this strategy. Here, we developed a glycosylated "triple-interaction" stabilized polymeric siRNA nanomedicine (Gal-NP@siRNA) to target BACE1 in APP/PS1 transgenic AD mouse model. Gal-NP@siRNA exhibits superior blood stability and can efficiently penetrate the blood-brain barrier (BBB) via glycemia-controlled glucose transporter-1 (Glut1)-mediated transport, thereby ensuring that siRNAs decrease BACE1 expression and modify relative pathways. Noticeably, Gal-NP@siBACE1 administration restored the deterioration of cognitive capacity in AD mice without notable side effects. This "Trojan horse" strategy supports the utility of RNA interference therapy in neurodegenerative diseases.
dc.languageEnglish
dc.publisherAMER ASSOC ADVANCEMENT SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.titleBlood-brain barrier-penetrating siRNA nanomedicine for Alzheimer's disease therapy
dc.typeJournal Article
dc.identifier.doi10.1126/sciadv.abc7031
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.source.titleScience Advances
melbourne.source.volume6
melbourne.source.issue41
dc.rights.licenseCC BY-NC
melbourne.elementsid1468452
melbourne.contributor.authorBush, Ashley
melbourne.contributor.authorShimoni, Olga
dc.identifier.eissn2375-2548
melbourne.accessrightsOpen Access


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