{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:59:18Z","timestamp":1787165958810,"version":"build-2736575974"},"reference-count":57,"publisher":"SAGE Publications","issue":"15-16","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>\n                    Choroideremia, an incurable, progressive retinal degeneration primarily affecting young men, leads to sight loss. GEMINI was a multicenter, open-label, prospective, two-period, interventional Phase II study assessing the safety of bilateral sequential administration of timrepigene emparvovec, a gene therapy, in adult males with genetically confirmed choroideremia (NCT03507686, ClinicalTrials.gov). Timrepigene emparvovec is an adeno-associated virus serotype 2 vector encoding the cDNA of Rab escort protein 1, augmented by a downstream woodchuck hepatitis virus post-transcriptional regulatory element. Up to 0.1 mL of timrepigene emparvovec, containing 1 \u00d7 10\n                    <jats:sup>11<\/jats:sup>\n                    vector genomes, was administered by subretinal injection following vitrectomy and retinal detachment. The second eye was treated after an intrasurgery window of &lt;6, 6\u201312, or &gt;12 months. Each eye was followed at up to nine visits over 12 months. Overall, 66 participants received timrepigene emparvovec, and 53 completed the study. Visual acuity (VA) was generally maintained in both eyes, independent of intrasurgery window duration, even after bilateral retinal detachment and subretinal injection. Bilateral treatment was well tolerated, with predominantly mild or moderate treatment-emergent adverse events (TEAEs) and a low rate of serious surgical complications (7.6%). Retinal inflammation TEAEs were reported in 45.5% of participants, with similar rates in both eyes;\n                    <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                    analyses found that these were not associated with clinically significant vision loss at month 12 versus baseline. Two participants (3.0%) reported serious noninfective retinitis. Prior timrepigene emparvovec exposure did not increase the risk of serious TEAEs or serious ocular TEAEs upon injection of the second eye; furthermore, no systemic immune reaction or inoculation effect was observed. Presence of antivector neutralizing antibodies at baseline was potentially associated with a higher percentage of TEAEs related to ocular inflammation or reduced VA after injection of the first eye. The GEMINI study results may inform decisions regarding bilateral sequential administration of other gene therapies for retinal diseases.\n                  <\/jats:p>","DOI":"10.1089\/hum.2024.017","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T06:13:18Z","timestamp":1720246398000},"page":"564-575","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["An Open-Label Phase II Study Assessing the Safety of Bilateral, Sequential Administration of Retinal Gene Therapy in Participants with Choroideremia: The GEMINI Study"],"prefix":"10.1177","volume":"35","author":[{"given":"Robert E.","family":"MacLaren","sequence":"first","affiliation":[{"name":"Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"},{"name":"Oxford NIHR Biomedical Research Centre, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Audo","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision, Paris, France"},{"name":"Centre Hospitalier National d\u2019Ophtalmologie des Quinze-Vingts, Centre de R\u00e9f\u00e9rence Maladies Rares REFERET and INSERM-DGOS CIC 1423, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Dominik","family":"Fischer","sequence":"additional","affiliation":[{"name":"University Eye Hospital, Centre for Ophthalmology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Huckfeldt","sequence":"additional","affiliation":[{"name":"MEE Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron L.","family":"Lam","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Pennesi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Casey Eye Institute, Oregon Health &amp; Science University, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sisk","sequence":"additional","affiliation":[{"name":"Cincinnati Eye Institute, Blue Ash, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Gow","sequence":"additional","affiliation":[{"name":"Biogen Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Biogen Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Biogen Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Fai","family":"Tsang","sequence":"additional","affiliation":[{"name":"Biogen Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.3410\/B2-3"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00296"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2014.12.022"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S364200"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2011.060"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/2515841418817490"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041279"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2020-316528"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/17469899.2019.1699406"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v12.i4.437"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13210"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22486"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2019.06.002"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000002553"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2020.03.003"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/IIO.0000000000000385"},{"issue":"1","key":"e_1_3_8_18_2","first-page":"179","article-title":"Choroideremia: A hereditary and clinical study","volume":"43","author":"McCulloch C","year":"1950","unstructured":"McCulloch C, , McCulloch RJP. 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