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Using a histone H3 tail-Dnmt3l fusion, CHARM recruits and activates endogenous DNA methyltransferases, thereby reducing transgene size and cytotoxicity. When delivered to the mouse brain by systemic injection of adeno-associated virus (AAV),\n                    <jats:italic>Prnp<\/jats:italic>\n                    -targeted CHARM ablates PrP expression across the brain. Furthermore, we have temporally limited editor expression by implementing a kinetically tuned self-silencing approach. CHARM potentially represents a broadly applicable strategy to suppress pathogenic proteins, including those implicated in other neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1126\/science.ado7082","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T14:01:31Z","timestamp":1719496891000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":130,"title":["Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor"],"prefix":"10.1126","volume":"384","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4341-9816","authenticated-orcid":true,"given":"Edwin N.","family":"Neumann","sequence":"first","affiliation":[{"name":"Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA."},{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, 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