{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:11:19Z","timestamp":1788343879727,"version":"build-2803163510"},"reference-count":37,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"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":["Nucleic Acid Therapeutics"],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:p>\n                    Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy most frequently associated with\n                    <jats:italic toggle=\"yes\">OPA1<\/jats:italic>\n                    mutations. Most variants result in haploinsufficiency, and patient cells express roughly half of the normal levels of OPA1 protein. OPA1 is a mitochondrial GTPase that is essential for normal mitochondrial function. We identified and characterized STK-002, an antisense oligonucleotide (ASO) designed to prevent the incorporation of a naturally occurring alternatively spliced nonproductive exon in\n                    <jats:italic toggle=\"yes\">OPA1<\/jats:italic>\n                    . STK-002 dose dependently reduced the inclusion of this exon, and increased OPA1 protein in human cells, including ADOA patient-derived fibroblasts. ADOA patient cells manifest reduced mitochondrial respiration, and treatment with STK-002 improved the parameters of mitochondrial respiratory function in these cells. Since STK-002 increases OPA1 through the wild-type allele, we assessed retinal OPA1 in wild-type cynomolgus monkeys and rabbits after intravitreal administration of STK-002 or a rabbit-specific surrogate. Increased OPA1 protein was produced in retinal tissue in both species at 4 weeks after ASO injection and persisted in monkeys at 8 weeks. STK-002 and enhanced OPA1 immunofluorescence were visualized in retinal ganglion cells of cynomolgus monkeys treated with the ASO. Cumulatively, these data support the progression of STK-002 toward the clinic as the first potential disease-modifying treatment for ADOA.\n                  <\/jats:p>","DOI":"10.1089\/nat.2024.0022","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T13:16:02Z","timestamp":1726146962000},"page":"221-233","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Antisense Oligonucleotide STK-002 Increases OPA1 in Retina and Improves Mitochondrial Function in Autosomal Dominant Optic Atrophy Cells"],"prefix":"10.1177","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-3414","authenticated-orcid":false,"given":"Aditya","family":"Venkatesh","sequence":"first","affiliation":[{"name":"Stoke Therapeutics, Bedford, Massachusetts, 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