{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:11:03Z","timestamp":1778875863127,"version":"3.51.4"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01 EY026177;,R21,EY034333,R01EY030366"],"award-info":[{"award-number":["R01 EY026177;,R21,EY034333,R01EY030366"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007817","name":"Alcon Research Institute","doi-asserted-by":"crossref","award":["Senior grant award"],"award-info":[{"award-number":["Senior grant award"]}],"id":[{"id":"10.13039\/100007817","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"crossref","award":["Stein Innovation award"],"award-info":[{"award-number":["Stein Innovation award"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:p>\n                    Mutations in\n                    <jats:italic>MYOC<\/jats:italic>\n                    , the most common genetic cause of glaucoma, cause misfolded myocilin to accumulate in the endoplasmic reticulum (ER), leading to trabecular meshwork (TM) dysfunction, elevated intraocular pressure, and progressive vision loss. While gene editing offers curative potential, current delivery methods rely on viral vectors, which are limited by inflammation, off-target effects, and poor translatability. Here, we report a nonviral lipid nanoparticle (LNP) platform that enables selective in vivo delivery of mRNA encoding an adenine base editor and single guide RNA (LNP-ABE) to TM cells. A direct comparison of LNP-mCherry with lentiviral GFP revealed that LNPs outperform viral vectors, achieving markedly higher efficiency and greater selectivity for the TM without inducing ocular inflammation. In a Cre-inducible\n                    <jats:italic>\n                      <jats:italic>\n                        Tg.CreMYOC\n                        <jats:sup>Y437H<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:italic>\n                    glaucoma mouse model, LNP-Cre mRNA selectively induced mutant\n                    <jats:italic>\n                      <jats:italic>MYOC<\/jats:italic>\n                    <\/jats:italic>\n                    expression in the TM, faithfully recapitulating key disease features. A single administration of LNP-ABE achieved efficient on-target editing of mutant\n                    <jats:italic>\n                      <jats:italic>MYOC<\/jats:italic>\n                    <\/jats:italic>\n                    , reducing mutant myocilin protein by approximately 46%, decreasing aggregates, alleviating ER stress, and fully rescuing the glaucomatous phenotype in\n                    <jats:italic>\n                      <jats:italic>\n                        Tg.CreMYOC\n                        <jats:sup>Y437H<\/jats:sup>\n                      <\/jats:italic>\n                    <\/jats:italic>\n                    mice. Importantly, no off-target editing or ocular toxicity was detected. These findings establish LNP-based mRNA delivery as a safe, efficient, and clinically translatable approach for TM-targeted genome editing with broad therapeutic potential in glaucoma.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.195593","type":"journal-article","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T19:00:48Z","timestamp":1770577248000},"source":"Crossref","is-referenced-by-count":1,"title":["Lipid-nanoparticle-mediated base editing of the trabecular meshwork rescues glaucoma in vivo"],"prefix":"10.1172","volume":"11","author":[{"given":"Balasankara Reddy","family":"Kaipa","sequence":"first","affiliation":[{"name":"Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of Ophthalmology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linya","family":"Li","sequence":"additional","affiliation":[{"name":"Gavin Herbert Eye Institute-Center for Translational Vision Research, Department of 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