{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:29:00Z","timestamp":1789770540309,"version":"4.0.1"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"36","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,9,5]]},"abstract":"<jats:p>\n            Subretinal injection of adeno-associated virus (AAV) is generally more efficacious and less inflammatory than intravitreal injection for retinal gene therapy. However, adverse events (e.g., chorioretinal atrophy) have been reported in many patients receiving subretinal injection of Luxturna (voretigene neparvovec-rzyl) and experimental gene therapies. Subretinal injection confines transduction to the treated area. To address this, we manufactured high-concentration fibrin hydrogels encapsulating AAV2\u2013green fluorescent protein (AAV2-\n            <jats:italic toggle=\"yes\">GFP<\/jats:italic>\n            ). Gels had homogeneous AAV distribution, desired mechanical properties, and retained infectivity. Epiretinal placement of fibrin\u2013AAV2-\n            <jats:italic toggle=\"yes\">GFP<\/jats:italic>\n            (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a011) was compared to subretinal (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a05) and intravitreal AAV2-\n            <jats:italic toggle=\"yes\">GFP<\/jats:italic>\n            injection (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a03). The subretinal group exhibited inconsistent retinal pigment epithelium (RPE) transduction restricted to the injection region with severe atrophy in two cases. The intravitreal group had weak transduction and inflammation. In contrast, epiretinal hydrogels degraded within days and led to broad transduction of RPE without atrophy or inflammation. This technology could advance gene therapy for retinal degenerations and other ocular or systemic disorders.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adv7922","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T17:58:29Z","timestamp":1757095109000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Retinal gene therapy using epiretinal AAV-containing fibrin hydrogel implants"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8806-1438","authenticated-orcid":true,"given":"Brittni A.","family":"Scruggs","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."},{"name":"Department of Pediatrics, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1913-3502","authenticated-orcid":true,"given":"Aubrey","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."},{"name":"Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca N.","family":"Kopp","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3806-7477","authenticated-orcid":true,"given":"Emma","family":"Trncic","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjersten","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5126-1898","authenticated-orcid":true,"given":"Raymond","family":"Iezzi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0363-2399","authenticated-orcid":true,"given":"Alan D.","family":"Marmorstein","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"53","article-title":"Voretigene neparvovec-rzyl (Luxturna) for inherited retinal dystrophy","volume":"60","year":"2018","unstructured":"Voretigene neparvovec-rzyl (Luxturna) for inherited retinal dystrophy. 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