{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:32:55Z","timestamp":1793197975365,"version":"4.5.0"},"reference-count":50,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["P30-EY001583"],"award-info":[{"award-number":["P30-EY001583"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["RO1-EY006855"],"award-info":[{"award-number":["RO1-EY006855"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Foundation Fighting Blindness","award":["Penn Large Animal Model Translational & Research C"],"award-info":[{"award-number":["Penn Large Animal Model Translational & Research C"]}]},{"name":"OPUS Genetics Inc","award":["Sponsored Research Agreement"],"award-info":[{"award-number":["Sponsored Research Agreement"]}]},{"name":"Iveric Bio Inc.","award":["Sponsored Research Agreement"],"award-info":[{"award-number":["Sponsored Research Agreement"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    To treat patients affected with bestrophinopathies caused by mutations in the\n                    <jats:italic toggle=\"yes\">BEST1<\/jats:italic>\n                    gene, a recombinant adeno-associated virus vector (OPGx-BEST1 or rAAV2\/2-VMD2-\n                    <jats:italic toggle=\"yes\">BEST1<\/jats:italic>\n                    ) is being developed. The vector construct includes the human BEST1 cDNA under control of the VMD2\/BEST1 promoter and is packaged in an AAV2 capsid. This study evaluated the efficacy and toxicity of OPGx-BEST1 administered by subretinal injection in dogs that were homozygous mutant or compound heterozygotes for 3 naturally occurring mutations in\n                    <jats:italic toggle=\"yes\">BEST1<\/jats:italic>\n                    . Twelve BEST1-mutant dogs were divided into 4 groups of 3 animals each, and they received in their left eye a subretinal injection of 0.15 mL of OPGx-BEST1 at 1 of 3 concentrations (9.5 \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    vector genome [vg]\/mL; 3.0 \u00d7 10\n                    <jats:sup>10<\/jats:sup>\n                    vg\/mL; or 3.0 \u00d7 10\n                    <jats:sup>11<\/jats:sup>\n                    vg\/mL) of OPGx-BEST1, resulting, respectively, in a low (1.4 \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    vg), high (4.5 \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    vg), and highest (4.5 \u00d7 10\n                    <jats:sup>10<\/jats:sup>\n                    vg) dose or vehicle control. The right eyes were not injected. Subretinal injections were well tolerated and were not associated with any systemic or ocular toxicity. Electroretinography showed improved rod- and cone-mediated responses in eyes treated with OPGx-BEST1. Noninvasive retinal imaging by optical coherence tomography showed improved structural integrity with a reduction or prevention of appearance of vitelliform lesions and reversal of microdetachments in the retinal areas treated with OPGx-BEST1. These results support the use of OPGx-BEST1 in clinical studies with patients affected with bestrophinopathies and define the no-observed-adverse-effect level at 4.5 \u00d7 10\n                    <jats:sup>10<\/jats:sup>\n                    vg\/eye (0.15 mL, 3.0 \u00d7 10\n                    <jats:sup>11<\/jats:sup>\n                    vg\/mL).\n                  <\/jats:p>","DOI":"10.1177\/10430342261458076","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:45:09Z","timestamp":1783406709000},"page":"876-886","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the Toxicity and Efficacy of an Adeno-Associated Viral Vector Expressing\n                    <i>BEST1<\/i>\n                    Delivered by Subretinal Injection in a Canine Model of Human Bestrophinopathy"],"prefix":"10.1177","volume":"37","author":[{"given":"Alexa","family":"Gray","sequence":"first","affiliation":[{"name":"Division of Experimental Retinal Therapies, Department of Clinical Sciences &amp; 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