{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:51:06Z","timestamp":1792036266514,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","issue":"57","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), driving A\u03b2 accumulation, tau pathology, and synaptic dysfunction. Allele\u2010specific correction of APOE4 represents a promising therapeutic strategy to mitigate disease progression. In this study, we developed an APOE4\u2010specific prime editing strategy based on an optimized APOE4\u2010targeting pegRNA, enabling precise and efficient conversion of the APOE4 allele to the lower\u2010risk APOE3 variant. We found that PE7 targeting the APOE4 allele achieved robust and specific editing without detectable off\u2010target effects. This correction reduced ApoE4 protein levels and attenuated key AD\u2010related pathologies, including A\u03b242 accumulation, tau phosphorylation, and activation of the ERK1\/2 pathway in APP\/APOE4 knock\u2010in (KI) mice. Notably, PE7 treatment enhanced neuronal survival and improved cognitive performance in these mice. Furthermore, in human induced neurons derived from APOE3\/4 heterozygous AD patient fibroblasts, PE7 consistently corrected the APOE4 allele and suppressed both amyloid\u2010 and tau\u2010associated pathologies. These findings establish PE7\u2010mediated APOE4 correction as a precise and efficient therapeutic genome\u2010editing strategy with translational potential for sporadic AD.<\/jats:p>","DOI":"10.1002\/advs.76658","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T20:43:59Z","timestamp":1784321039000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Gene Editing of APOE4 in Sporadic Alzheimer's Disease via Prime Editor 7"],"prefix":"10.1002","volume":"13","author":[{"given":"Yunkyung","family":"Kim","sequence":"first","affiliation":[{"name":"Institute for Stem Cells and Regenerative Medicine (ISR) Department of Chemistry Dongguk University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaeun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology Sungkyunkwan University  Suwon 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