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To overcome this, we introduce Biodegradable Acoustic Targeting for Ultrasound\u2010Supported Gene Therapy (BATUS), a modular platform that enables safe, repeated, and targeted gene delivery to the brain. BATUS integrates an implantable, fully biodegradable glycine\u2010based ultrasound (US) transducer, surgically placed via craniotomy for precise BBB opening, along with customizable peptide\u2010targeted liposomal gene carriers. This system combines US\u2010mediated transient BBB disruption with ligand\u2010directed cellular targeting to enable efficient delivery across both vascular and cellular barriers. As a proof\u2010of\u2010concept, BATUS was evaluated using tLyp1\u2010functionalized liposomes carrying PD\u2010L1\u2010targeting siRNA for GBM immunotherapy: in vitro evaluations confirmed efficient siRNA entrapment, stability, and specific cellular uptake, while in vivo studies in orthotopic GL261 GBM mouse models showed enhanced BBB permeability, significant PD\u2010L1 silencing, reduced tumor growth, and prolonged survival. Crucially, BATUS exhibited a favorable safety profile, with no detectable local or systemic toxicity in animal models. By providing a modular framework where targeting ligands and genetic cargo are easily adaptable, BATUS is established as a strategy for precision gene delivery across the BBB, as demonstrated here for GBM.<\/jats:p>","DOI":"10.1002\/advs.76336","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T16:48:14Z","timestamp":1782751694000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biodegradable Acoustic Targeting for Ultrasound\u2010Supported Gene Therapy (BATUS) in Glioblastoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Gulsah","family":"Erel\u2010Akbaba","sequence":"first","affiliation":[{"name":"Polymer Program Institute of Materials Science University of Connecticut  Storrs Connecticut USA"},{"name":"Department of Pharmaceutical Biotechnology Faculty of Pharmacy Izmir Katip Celebi University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0943-3649","authenticated-orcid":false,"given":"Jinyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achal","family":"Duhoon","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao Thuy Giang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Polymer Program Institute of Materials Science University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitu","family":"Bhaskar","sequence":"additional","affiliation":[{"name":"Center for Clean Energy Engineering University of Connecticut  Storrs CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-3946","authenticated-orcid":false,"given":"Sumanta Kumar","family":"Karan","sequence":"additional","affiliation":[{"name":"Center for Clean Energy Engineering University of Connecticut  Storrs CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Akbaba","sequence":"additional","affiliation":[{"name":"Polymer Program Institute of Materials Science University of Connecticut  Storrs Connecticut USA"},{"name":"Ege University Vaccine Development Application and Research Center  Izmir Turkey"},{"name":"Department of Pharmaceutical Biotechnology Faculty of Pharmacy Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parbeen","family":"Singh","sequence":"additional","affiliation":[{"name":"Polymer Program Institute of Materials Science University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Bao Tram","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Polymer Program Institute of Materials Science University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I'jaaz","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang Quan","family":"Truong","sequence":"additional","affiliation":[{"name":"Polymer Program Institute of Materials Science University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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