{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:05:25Z","timestamp":1784729125584,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,14]]},"group-title":"Bioengineering","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>\n                    Oculocutaneous albinism type 1 (OCA1) is an inherited disorder caused by tyrosinase (\n                    <jats:italic>TYR<\/jats:italic>\n                    ) gene mutations. Affected individuals experience visual impairment and severe photosensitivity from ocular hypomelanosis, with no current treatments. We evaluated the safety and efficacy of a\n                    <jats:italic>TYR<\/jats:italic>\n                    -encoding adeno-associated virus (AAV) vector in healthy rhesus macaques as a potential OCA1 treatment.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    A novel AAV2-based capsid (ATX002) was packaged with the human VMD2 promoter and\n                    <jats:italic>TYR<\/jats:italic>\n                    (h\n                    <jats:italic>TYR<\/jats:italic>\n                    ) fused with mGreenLantern (mGL). Two adult rhesus macaques were injected with ATX002-hVMD2-h\n                    <jats:italic>TYR<\/jats:italic>\n                    -\n                    <jats:italic>mGL<\/jats:italic>\n                    subretinally (OD) and intravitreally (OS). Safety and efficacy were assessed via comprehensive ophthalmic examination, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinography at baseline and defined timepoints up to 12 weeks post-injection, followed by post-mortem immunohistochemistry (IHC).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Both subretinal doses induced localized hypermelanosis by 3 weeks post-injection, which persisted through the study endpoint and was accompanied by measurable thickening of the retinal pigment epithelium (RPE) on SD-OCT. Histological IHC confirmed successful RPE transduction via robust mGL fluorescence, corroborating\n                    <jats:italic>in vivo<\/jats:italic>\n                    findings by revealing localized RPE hyperplasia and transgene-expressing cells adjacent to regions of\n                    <jats:italic>de novo<\/jats:italic>\n                    hypermelanosis. Intravitreal delivery did not induce any changes to the RPE. Transient uveitis was observed but successfully managed with anti-inflammatory treatment.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Subretinal AAV-\n                    <jats:italic>TYR<\/jats:italic>\n                    delivery is a safe and effective approach with the potential to induce RPE pigmentation. These findings support the use of AAV-\n                    <jats:italic>TYR<\/jats:italic>\n                    gene therapy for OCA1, demonstrating efficacy and a manageable safety profile in a large-animal model, and provide a critical bridge toward human clinical translation.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.13.738268","type":"posted-content","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:35:13Z","timestamp":1784036113000},"source":"Crossref","is-referenced-by-count":0,"title":["Ocular Safety and Efficacy of AAV-mediated Tyrosinase Gene Augmentation in a Nonhuman Primate Model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1139-7018","authenticated-orcid":false,"given":"Jaegook","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra M.","family":"Larimer-Picciani","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala","family":"Moshiri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science, School of Medicine, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, TX, 75390, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyoshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, TX, 75390, United States"},{"name":"Department of Electrical and Computer Engineering, University of Texas at Dallas, Richardson, Texas, TX, 75080, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cl\u00e1udia Santos","family":"Raposo","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica J.","family":"Motta","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah C.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5617-9677","authenticated-orcid":false,"given":"Sara M.","family":"Thomasy","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"},{"name":"Department of Ophthalmology and Vision Science, School of Medicine, University of California Davis, Davis, CA 95616, USA"},{"name":"National Biomedical Research Institute, University of California, Davis, Davis, CA, 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"1","key":"2026072206401334000_2026.07.13.738268v2.1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1750-1172-2-43","article-title":"Oculocutaneous albinism","volume":"2","year":"2007","journal-title":"Orphanet journal of rare 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