{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:16:30Z","timestamp":1791346590101,"version":"4.3.1"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Materials"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    CRISPR genome editing can\u00a0potentially treat the root causes of many genetic diseases, including central nervous system (CNS) disorders. However, the promise of brain\u2010targeted therapeutic genome editing relies on the efficient delivery of biologics bypassing the blood\u2013brain barrier (BBB), which represents a major challenge in the development of CRISPR therapeutics.\u00a0We\u00a0created and screened\u00a0a library of glutathione (GSH)\u2010responsive silica nanocapsules (SNCs) for brain targeted delivery of biologics via systemic administration. In vivo studies demonstrate that systemically delivered SNCs conjugated with glucose and rabies virus glycoprotein peptide under glycemic control can efficiently bypass the intact BBB, enabling brain\u2010wide delivery of various biologics including CRISPR genome editors targeting different genes in both Ai14 reporter mice and wild\u2010type mice. In particular, up to 28% neuron editing via systemic delivery of Cre mRNA in Ai14 mice, up to 6.1% amyloid precursor protein (\n                    <jats:italic>App<\/jats:italic>\n                    ) gene editing (resulting in 19.1% reduction in the expression level of intact APP), and up to 3.9% tyrosine hydroxylase (\n                    <jats:italic>Th<\/jats:italic>\n                    ) gene editing (resulting in 30.3% reduction in the expression level of TH) in wild\u2010type mice are observed. This versatile SNC nanoplatform may offer a novel strategy for the treatment of CNS disorders including Alzheimer's, Parkinson's, and Huntington's disease.\n                  <\/jats:p>","DOI":"10.1002\/adma.202208018","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T09:55:30Z","timestamp":1669715730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Overcoming the Blood\u2013Brain Barrier for Gene Therapy via Systemic Administration of GSH\u2010Responsive Silica Nanocapsules"],"prefix":"10.1002","volume":"35","author":[{"given":"Yuyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences University of Wisconsin\u2010Madison  Madison WI 53705 USA"},{"name":"Department of Biomedical Engineering University of Wisconsin\u2010Madison  Madison WI 53706 USA"},{"name":"Wisconsin Institute for Discovery University of 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