{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T03:04:52Z","timestamp":1780628692916,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["2R44EY025905-02A1"],"award-info":[{"award-number":["2R44EY025905-02A1"]}]},{"name":"National Institute of Health","award":["1R01EY025717-01A1"],"award-info":[{"award-number":["1R01EY025717-01A1"]}]},{"name":"National Institute of Health","award":["1R01EY028216-01A1"],"award-info":[{"award-number":["1R01EY028216-01A1"]}]},{"name":"Nanoscope Therapeutics, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Optogenetic gene therapy-based treatment offers a unique approach to bypass dysfunctional or degenerated photoreceptors in retinal degenerative disorders. Ambient light-activatable multi-characteristic opsin (MCO) targeted to bipolar cells of the retina has demonstrated partial vision restoration in animal models of retinitis pigmentosa (RP). Here, we describe the potential therapeutic efficacy of intravitreally delivered AAV-carried MCO-010 in a mouse model of Stargardt disease. MCO-010 treatment led to significantly improved behavioral outcomes in the visually guided radial arm water maze. Furthermore, longitudinal optical coherence tomographic imaging showed that the MCO-010 treatment led to no notable change in the retina thickness. Furthermore, the MCO-010-treated mice exhibited higher electrophysiological responses compared to the control group. Together, these findings demonstrate potential vision-restoring and disease-modifying aspects of ambient light-activatable intravitreal MCO-010 therapy.<\/jats:p>","DOI":"10.3390\/bioengineering13060660","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:23:21Z","timestamp":1780622601000},"page":"660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Efficacy of Multi-Characteristic Opsin Gene Therapy in a Mouse Model of Stargardt Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Samarendra","family":"Mohanty","sequence":"first","affiliation":[{"name":"Nanoscope Therapeutics Inc., 2777 N. Stemmons Fwy, Dallas, TX 75207, USA"},{"name":"Nanoscope Technologies LLC., 1312 Brown Trail, Bedford, TX 76022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0859-6641","authenticated-orcid":false,"given":"Subrata","family":"Batabyal","sequence":"additional","affiliation":[{"name":"Nanoscope Technologies LLC., 1312 Brown Trail, Bedford, TX 76022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanghoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Nanoscope Technologies LLC., 1312 Brown Trail, Bedford, TX 76022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Carlson","sequence":"additional","affiliation":[{"name":"Nanoscope Technologies LLC., 1312 Brown Trail, Bedford, TX 76022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Dibas","sequence":"additional","affiliation":[{"name":"Nanoscope Technologies LLC., 1312 Brown Trail, Bedford, TX 76022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tsang, S.H., and Sharma, T. (2018). Stargardt disease. Advances in Experimental Medicine and Biology, Springer.","DOI":"10.1007\/978-3-319-95046-4_27"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Al-Khuzaei, S., Broadgate, S., Foster, C.R., Shah, M., Yu, J., Downes, S.M., and Halford, S. (2021). An overview of the genetics of ABCA4 retinopathies, an evolving story. Genes, 12.","DOI":"10.3390\/genes12081241"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tsybovsky, Y., Molday, R.S., and Palczewski, K. (2010). The ATP-binding cassette transporter ABCA4: Structural and functional properties and role in retinal disease. Inflammation and Retinal Disease: Complement Biology and Pathology, Springer.","DOI":"10.1007\/978-1-4419-5635-4_8"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1055\/a-1057-9939","article-title":"ABCA4-associated Stargardt disease","volume":"237","author":"Khan","year":"2020","journal-title":"Klin. Monatsbl\u00e4tter Augenheilkd."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1136\/bjophthalmol-2016-308823","article-title":"Stargardt disease: Clinical features, molecular genetics, animal models and therapeutic options","volume":"101","author":"Tanna","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"R\u00f3\u017canowska, M.B. (2023). Lipofuscin, its origin, properties, and contribution to retinal fluorescence as a potential biomarker of oxidative damage to the retina. Antioxidants, 12.","DOI":"10.20944\/preprints202307.0304.v1"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nebbioso, M., Franzone, F., Lambiase, A., Bonfiglio, V., Limoli, P.G., Artico, M., Taurone, S., Vingolo, E.M., Greco, A., and Polimeni, A. (2022). Oxidative stress implication in retinal diseases\u2014A review. Antioxidants, 11.","DOI":"10.3390\/antiox11091790"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13578-024-01272-y","article-title":"The ABCs of Stargardt disease: The latest advances in precision medicine","volume":"14","author":"Zaydon","year":"2024","journal-title":"Cell Biosci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Han, Z., Conley, S.M., and Naash, M.I. (2014). Gene therapy for Stargardt disease associated with ABCA4 gene. Retinal Degenerative Diseases, Springer.","DOI":"10.1007\/978-1-4614-3209-8_90"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13816810.2021.1966053","article-title":"Stargardt disease and progress in therapeutic strategies","volume":"43","author":"Huang","year":"2022","journal-title":"Ophthalmic Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8538","DOI":"10.1073\/pnas.1701083114","article-title":"A promiscuous split intein with expanded protein engineering applications","volume":"114","author":"Stevens","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1258096","DOI":"10.1126\/science.1258096","article-title":"The new frontier of genome engineering with CRISPR-Cas9","volume":"346","author":"Doudna","year":"2014","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.omtn.2023.02.032","article-title":"Efficient correction of Abca4 variants by CRISPR-Cas9 in hiPSCs derived from stargardt disease patients","volume":"32","author":"Siles","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41434-024-00455-z","article-title":"Retinoic acid related orphan receptor \u03b1 is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD","volume":"31","author":"Akula","year":"2024","journal-title":"Gene Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12934-019-1058-4","article-title":"Engineering the flagellar type III secretion system: Improving capacity for secretion of recombinant protein","volume":"18","author":"Green","year":"2019","journal-title":"Microb. Cell Factories"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Tripathi, N.K., and Shrivastava, A. (2019). Recent developments in bioprocessing of recombinant proteins: Expression hosts and process development. Front. Bioeng. Biotechnol., 7.","DOI":"10.3389\/fbioe.2019.00420"},{"key":"ref_17","first-page":"041505","article-title":"Restoring vision in mice with retinal degeneration using multicharacteristic opsin","volume":"4","author":"Wright","year":"2017","journal-title":"Neurophotonics"},{"key":"ref_18","first-page":"2137","article-title":"Longitudinal BCVA analysis of low-or high-dose MCO-010 mutation agnostic optogenetic therapy for retinitis pigmentosa: 12-month results from a Phase 2b\/3 randomized, sham-controlled, patient-and assessor-masked clinical trial (RESTORE)","volume":"65","author":"Ho","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0092-8674(00)80602-9","article-title":"Insights into the function of Rim protein in photoreceptors and etiology of Stargardt\u2019s disease from the phenotype in abcr knockout mice","volume":"98","author":"Weng","year":"1999","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8415","DOI":"10.1073\/pnas.1506960112","article-title":"Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization","volume":"112","author":"Barnard","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.exer.2009.03.005","article-title":"Focus on molecules: ABCA4 (ABCR)\u2014An import-directed photoreceptor retinoid flipase","volume":"89","author":"Sullivan","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1086\/303090","article-title":"A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration","volume":"67","author":"Rivera","year":"2000","journal-title":"Am. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101036","DOI":"10.1016\/j.preteyeres.2021.101036","article-title":"Structure and function of ABCA4 and its role in the visual cycle and Stargardt macular degeneration","volume":"89","author":"Molday","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E11120","DOI":"10.1073\/pnas.1802519115","article-title":"Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration","volume":"115","author":"Lenis","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","unstructured":"Zhong, M. (2009). ABCA4 Structure-Function Relationships: Role in Stargardt Disease and Related Retinal Degenerative Diseases. [Ph.D. Thesis, University of British Columbia]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1167\/tvst.13.10.25","article-title":"Multi-Characteristic Opsin Therapy to Functionalize Retina, Attenuate Retinal Degeneration, and Restore Vision in Mouse Models of Retinitis Pigmentosa","volume":"13","author":"Batabyal","year":"2024","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5000","DOI":"10.1523\/JNEUROSCI.5800-10.2011","article-title":"An intrinsic neural oscillator in the degenerating mouse retina","volume":"31","author":"Borowska","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41434-020-00200-2","article-title":"Sensitization of ON-bipolar cells with ambient light activatable multi-characteristic opsin rescues vision in mice","volume":"28","author":"Batabyal","year":"2021","journal-title":"Gene Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S1350-9462(03)00039-9","article-title":"Neural remodeling in retinal degeneration","volume":"22","author":"Marc","year":"2003","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s42003-022-04016-1","article-title":"Bipolar cell targeted optogenetic gene therapy restores parallel retinal signaling and high-level vision in the degenerated retina","volume":"5","author":"Kralik","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107716","DOI":"10.1016\/j.isci.2023.107716","article-title":"Highly sensitive visual restoration and protection via ectopic expression of chimeric rhodopsin in mice","volume":"26","author":"Katada","year":"2023","journal-title":"Iscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2500056","DOI":"10.1080\/19490976.2025.2500056","article-title":"Engineered bacteria as an orally administered anti-viral treatment and immunization system","volume":"17","author":"Kamble","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8676","DOI":"10.1111\/jcmm.16823","article-title":"Biodistribution of adeno-associated virus type 2 carrying multi-characteristic opsin in dogs following intravitreal injection","volume":"25","author":"Tchedre","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e3720","DOI":"10.1002\/jgm.3720","article-title":"Safety of intravitreally delivered AAV2 vector-mediated multi-characteristic opsin genetic construct in wild type beagle dogs","volume":"26","author":"Mohanty","year":"2024","journal-title":"J. Gene Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2202870","DOI":"10.1002\/adhm.202202870","article-title":"An engineered probiotic platform for cancer epitope-independent targeted radionuclide therapy of solid tumors","volume":"12","author":"Siddiqui","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103430","DOI":"10.1016\/j.eclinm.2025.103430","article-title":"Safety and efficacy of MCO-010 optogenetic therapy in patients with Stargardt disease in USA (STARLIGHT): An open-label multi-center Ph2 trial","volume":"87","author":"Lam","year":"2025","journal-title":"EClinicalMedicine"}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/6\/660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:25:56Z","timestamp":1780626356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/6\/660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["bioengineering13060660"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13060660","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]}}}