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Small interfering RNAs (siRNA) have shown great potential for disease treatment by specifically silencing target genes. However, the poor brain delivery efficiency of siRNAs limits their therapeutic efficacy against AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We designed a simplified and effective\n                      <jats:italic>BACE1<\/jats:italic>\n                      siRNA (siBACE1) delivery system, namely, dendritic polyamidoamine modified with the neurotropic virus-derived peptide RVG29 and polyethylene glycol (PPR@siBACE1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PPR@siBACE1 crossed the blood\u2013brain barrier efficiently and entered brain parenchyma in large amount, with subsequent neurotropism and potential microglia-targeting ability. Both in vitro and in vivo studies validated the effective brain delivery of siBACE1 and strong\n                      <jats:italic>BACE1<\/jats:italic>\n                      silencing efficiency. Treatment of AD mice with PPR@siBACE1 inhibited the production of A\u03b2, potentiated A\u03b2 phagocytosis by microglia, improved the memory deficits and reduced neuroinflammatory response in AD mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides a reliable delivery platform for gene therapies for AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40035-025-00503-7","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T03:54:18Z","timestamp":1755143658000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Targeted delivery of BACE1 siRNA for synergistic treatment of Alzheimer's disease"],"prefix":"10.1186","volume":"14","author":[{"given":"Zhaohan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Qing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"503_CR1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.bioorg.2018.11.022","volume":"84","author":"Q Song","year":"2019","unstructured":"Song Q, Li Y, Cao Z, Qiang X, Tan Z, Deng Y. 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