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Lowering circulating IgG is a validated and promising therapeutic avenue. Here we developed\n                  <jats:underline>g<\/jats:underline>\n                  enetically-\n                  <jats:underline>e<\/jats:underline>\n                  ncoded lysosome targeting\n                  <jats:underline>c<\/jats:underline>\n                  himeras (GELYTACs) that target circulating IgGs for clearance and degradation. The GELYTACs comprised two protein modules derived from insulin-like growth factor 2 (IGF2) and an IgG-binding nanobody, respectively, and mediated clearance of plasma IgG via the lysosomal trafficking receptor IGF2R. To achieve long-lasting IgG depletion, we encoded GELYTACs in an AAV gene therapy vector and established continuous expression in mice. We also developed conditional GELYACs that are activatable with disease-specific proteases or small molecule drugs and show that GELYTACs can be secreted from cellular therapies. This work establishes GELYTACs as a possible therapeutic modality that is deliverable using genetic medicine approaches.\n                <\/jats:p>","DOI":"10.64898\/2026.07.05.736665","type":"posted-content","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T21:05:53Z","timestamp":1783371953000},"source":"Crossref","is-referenced-by-count":0,"title":["AAV delivered lysosome-targeting chimeras mediate sustained antibody depletion\n                  <i>in vivo<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3378-1379","authenticated-orcid":false,"given":"Jonathan Lee","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Chemistry, Stanford University, Stanford, CA 94305"},{"name":"Sarafan ChEM-H, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Yong","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Stanford University, Stanford, 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