{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:39:22Z","timestamp":1782977962572,"version":"3.54.5"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00453840"],"award-info":[{"award-number":["RS-2024-00453840"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019M3A9H1030948"],"award-info":[{"award-number":["NRF-2019M3A9H1030948"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-07299-6","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:32:34Z","timestamp":1753489954000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In vivo efficacy of NRL knockdown with cell-penetrating siRNA in retinal degeneration"],"prefix":"10.1038","volume":"15","author":[{"given":"Hyungwoo","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoik","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Byoung","family":"Chae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Kyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanok","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul-Woo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taejeong","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munjeong","family":"Yum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungmi","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Woo","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungmook","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Ki","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyewon","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"7299_CR1","doi-asserted-by":"publisher","first-page":"e015531","DOI":"10.1136\/bmjopen-2016-015531","volume":"7","author":"TH Rim","year":"2017","unstructured":"Rim, T. H., Park, H. W., Kim, D. W. & Chung, E. J. Four-year nationwide incidence of retinitis pigmentosa in South Korea: a population-based retrospective study from 2011 to 2014. BMJ Open. 7, e015531. https:\/\/doi.org\/10.1136\/bmjopen-2016-015531 (2017).","journal-title":"BMJ Open."},{"key":"7299_CR2","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1136\/bjophthalmol-2019-314422","volume":"104","author":"JQ Li","year":"2020","unstructured":"Li, J. Q. et al. Prevalence and incidence of age-related macular degeneration in Europe: a systematic review and meta-analysis. Br. J. Ophthalmol. 104, 1077\u20131084 (2020).","journal-title":"Br. J. Ophthalmol."},{"key":"7299_CR3","doi-asserted-by":"publisher","first-page":"e134","DOI":"10.1111\/aos.14483","volume":"99","author":"CL Teo","year":"2021","unstructured":"Teo, C. L. et al. Prevalence of retinitis pigmentosa in singapore: the Singapore Epidemiology of Eye Diseases Study. Acta Ophthalmol. 99, e134\u2013e135. https:\/\/doi.org\/10.1111\/aos.14483 (2021).","journal-title":"Acta Ophthalmol."},{"key":"7299_CR4","doi-asserted-by":"publisher","unstructured":"de Cabral, T. A., Daich Varela, M., Georgiou, M. & Michaelides, M. Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions. Br. J. Ophthalmol. 318452 https:\/\/doi.org\/10.1136\/bjophthalmol-2020-318452 (2021).","DOI":"10.1136\/bjophthalmol-2020-318452"},{"key":"7299_CR5","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1001\/jamaophthalmol.2019.1476","volume":"137","author":"K Schaffrath","year":"2019","unstructured":"Schaffrath, K. et al. One-Year safety and performance assessment of the Argus II retinal prosthesis: a postapproval study. JAMA Ophthalmol. 137, 896\u2013902 (2019).","journal-title":"JAMA Ophthalmol."},{"key":"7299_CR6","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/j.ophtha.2019.06.017","volume":"126","author":"AM Maguire","year":"2019","unstructured":"Maguire, A. M. et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation\u2013associated inherited retinal dystrophy: results of phase 1 and 3 trials. Ophthalmology 126, 1273\u20131285 (2019).","journal-title":"Ophthalmology"},{"key":"7299_CR7","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1038\/s41591-021-01351-4","volume":"27","author":"JA Sahel","year":"2021","unstructured":"Sahel, J. A. et al. Partial recovery of visual function in a blind patient after optogenetic therapy. Nat. Med. 27, 1223\u20131229. https:\/\/doi.org\/10.1038\/s41591-021-01351-4 (2021).","journal-title":"Nat. Med."},{"key":"7299_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.preteyeres.2018.11.001","volume":"69","author":"SJ Gasparini","year":"2019","unstructured":"Gasparini, S. J., Llonch, S., Borsch, O. & Ader, M. Transplantation of photoreceptors into the degenerative retina: current state and future perspectives. Prog. Retin. Eye Res. 69, 1\u201337 (2019).","journal-title":"Prog. Retin. Eye Res."},{"key":"7299_CR9","doi-asserted-by":"publisher","first-page":"109022","DOI":"10.1016\/j.celrep.2021.109022","volume":"35","author":"J Ribeiro","year":"2021","unstructured":"Ribeiro, J. et al. Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors. Cell. Rep. 35, 109022 (2021).","journal-title":"Cell. Rep."},{"key":"7299_CR10","doi-asserted-by":"crossref","unstructured":"Zerti, D. et al. Transplanted pluripotent stem cell-derived photoreceptor precursors elicit conventional and unusual light responses in mice with advanced retinal degeneration. Stem Cells (2021).","DOI":"10.1101\/2020.09.22.308726"},{"key":"7299_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms13537","volume":"7","author":"MS Singh","year":"2016","unstructured":"Singh, M. S. et al. Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion. Nat. Commun. 7, 1\u20135 (2016).","journal-title":"Nat. Commun."},{"key":"7299_CR12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.stemcr.2016.12.008","volume":"8","author":"M Mandai","year":"2017","unstructured":"Mandai, M. et al. iPSC-derived retina transplants improve vision in rd1 end-stage retinal-degeneration mice. Stem Cell. Rep. 8, 69\u201383 (2017).","journal-title":"Stem Cell. Rep."},{"key":"7299_CR13","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1136\/bjo.2006.113902","volume":"91","author":"A Lux","year":"2007","unstructured":"Lux, A., Llacer, H., Heussen, F. M. & Joussen, A. M. Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions. Br. J. Ophthalmol. 91, 1318\u20131322. https:\/\/doi.org\/10.1136\/bjo.2006.113902 (2007).","journal-title":"Br. J. Ophthalmol."},{"key":"7299_CR14","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.ophtha.2019.11.010","volume":"127","author":"SR Sadda","year":"2020","unstructured":"Sadda, S. R., Guymer, R., Mon\u00e9s, J. M., Tufail, A. & Jaffe, G. J. Anti\u2013vascular endothelial growth factor use and atrophy in neovascular age-related macular degeneration: systematic literature review and expert opinion. Ophthalmology 127, 648\u2013659 (2020).","journal-title":"Ophthalmology"},{"key":"7299_CR15","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.stem.2016.05.005","volume":"18","author":"M Rezvani","year":"2016","unstructured":"Rezvani, M. et al. In vivo hepatic reprogramming of myofibroblasts with AAV vectors as a therapeutic strategy for liver fibrosis. Cell. Stem Cell. 18, 809\u2013816 (2016).","journal-title":"Cell. Stem Cell."},{"key":"7299_CR16","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.stem.2016.01.010","volume":"18","author":"G Song","year":"2016","unstructured":"Song, G. et al. Direct reprogramming of hepatic myofibroblasts into hepatocytes in vivo attenuates liver fibrosis. Cell. Stem Cell. 18, 797\u2013808 (2016).","journal-title":"Cell. Stem Cell."},{"key":"7299_CR17","unstructured":"Wang, H., Yang, Y., Liu, J. & Qian, L. Direct cell reprogramming: approaches, mechanisms and progress. Nat Rev. Mol. Cell. Biol 2021, 1\u201315 (2021)."},{"key":"7299_CR18","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/0092-8674(87)90585-X","volume":"51","author":"RL Davis","year":"1987","unstructured":"Davis, R. L., Weintraub, H. & Lassar, A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987\u20131000 (1987).","journal-title":"Cell"},{"key":"7299_CR19","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.cell.2010.07.002","volume":"142","author":"M Ieda","year":"2010","unstructured":"Ieda, M. et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142, 375\u2013386 (2010).","journal-title":"Cell"},{"key":"7299_CR20","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/nature08797","volume":"463","author":"T Vierbuchen","year":"2010","unstructured":"Vierbuchen, T. et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035\u20131041 (2010).","journal-title":"Nature"},{"key":"7299_CR21","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/nature23283","volume":"548","author":"NL Jorstad","year":"2017","unstructured":"Jorstad, N. L. et al. Stimulation of functional neuronal regeneration from M\u00fcller glia in adult mice. Nature 548, 103\u2013107. https:\/\/doi.org\/10.1038\/nature23283 (2017).","journal-title":"Nature"},{"key":"7299_CR22","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/s41586-018-0425-3","volume":"560","author":"K Yao","year":"2018","unstructured":"Yao, K. et al. Restoration of vision after de Novo genesis of rod photoreceptors in mammalian retinas. Nature 560, 484\u2013488. https:\/\/doi.org\/10.1038\/s41586-018-0425-3 (2018).","journal-title":"Nature"},{"key":"7299_CR23","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/ng774","volume":"29","author":"AJ Mears","year":"2001","unstructured":"Mears, A. J. et al. Nrl is required for rod photoreceptor development. Nat. Genet. 29, 447\u2013452. https:\/\/doi.org\/10.1038\/ng774 (2001).","journal-title":"Nat. Genet."},{"key":"7299_CR24","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1073\/pnas.1214387110","volume":"110","author":"CL Montana","year":"2013","unstructured":"Montana, C. L. et al. Reprogramming of adult rod photoreceptors prevents retinal degeneration. Proc. Natl. Acad. Sci. U.S.A. 110, 1732\u20131737. https:\/\/doi.org\/10.1073\/pnas.1214387110 (2013).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"7299_CR25","doi-asserted-by":"publisher","first-page":"14716","DOI":"10.1038\/ncomms14716","volume":"8","author":"W Yu","year":"2017","unstructured":"Yu, W. et al. Nrl knockdown by AAV-delivered CRISPR\/Cas9 prevents retinal degeneration in mice. Nat. Commun. 8, 14716. https:\/\/doi.org\/10.1038\/ncomms14716 (2017).","journal-title":"Nat. Commun."},{"key":"7299_CR26","doi-asserted-by":"publisher","first-page":"3497","DOI":"10.1038\/s41467-018-05843-9","volume":"9","author":"JM Crudele","year":"2018","unstructured":"Crudele, J. M. & Chamberlain, J. S. Cas9 immunity creates challenges for CRISPR gene editing therapies. Nat. Commun. 9, 3497. https:\/\/doi.org\/10.1038\/s41467-018-05843-9 (2018).","journal-title":"Nat. Commun."},{"key":"7299_CR27","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s13059-018-1534-x","volume":"19","author":"F Alkan","year":"2018","unstructured":"Alkan, F., Wenzel, A., Anthon, C., Havgaard, J. H. & Gorodkin, J. CRISPR-Cas9 off-targeting assessment with nucleic acid duplex energy parameters. Genome Biol. 19, 177\u2013177. https:\/\/doi.org\/10.1186\/s13059-018-1534-x (2018).","journal-title":"Genome Biol."},{"key":"7299_CR28","first-page":"210","volume":"9","author":"SJ Reich","year":"2003","unstructured":"Reich, S. J. et al. Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Mol. Vis. 9, 210\u2013216 (2003).","journal-title":"Mol. Vis."},{"key":"7299_CR29","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/sj.gt.3302641","volume":"13","author":"J Shen","year":"2006","unstructured":"Shen, J. et al. Suppression of ocular neovascularization with SiRNA targeting VEGF receptor 1. Gene Ther. 13, 225\u2013234. https:\/\/doi.org\/10.1038\/sj.gt.3302641 (2006).","journal-title":"Gene Ther."},{"key":"7299_CR30","doi-asserted-by":"publisher","first-page":"3104","DOI":"10.2337\/db06-0519","volume":"55","author":"H Kaur","year":"2006","unstructured":"Kaur, H. et al. Diabetes-induced extracellular matrix protein expression is mediated by transcription coactivator p300. Diabetes 55, 3104\u20133111 (2006).","journal-title":"Diabetes"},{"key":"7299_CR31","doi-asserted-by":"publisher","first-page":"2977","DOI":"10.1167\/iovs.17-21672","volume":"58","author":"R Natoli","year":"2017","unstructured":"Natoli, R. et al. Retinal macrophages synthesize C3 and activate complement in AMD and in models of focal retinal degeneration. Invest. Ophthalmol. Vis. Sci. 58, 2977\u20132990 (2017).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"7299_CR32","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/j.1365-2362.2010.02400.x","volume":"41","author":"SH Chen","year":"2011","unstructured":"Chen, S. H. & Zhaori, G. Potential clinical applications of SiRNA technique: benefits and limitations. Eur. J. Clin. Invest. 41, 221\u2013232 (2011).","journal-title":"Eur. J. Clin. Invest."},{"key":"7299_CR33","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1002\/path.2993","volume":"226","author":"JK Watts","year":"2012","unstructured":"Watts, J. K. & Corey, D. R. Silencing disease genes in the laboratory and the clinic. J. Pathol. 226, 365\u2013379 (2012).","journal-title":"J. Pathol."},{"key":"7299_CR34","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1016\/j.jid.2016.06.626","volume":"136","author":"J Hwang","year":"2016","unstructured":"Hwang, J. et al. Development of cell-penetrating asymmetric interfering RNA targeting connective tissue growth factor. J. Invest. Dermatology. 136, 2305\u20132313 (2016).","journal-title":"J. Invest. Dermatology"},{"key":"7299_CR35","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/mt.2008.298","volume":"17","author":"CI Chang","year":"2009","unstructured":"Chang, C. I. et al. Asymmetric shorter-duplex SiRNA structures trigger efficient gene Silencing with reduced nonspecific effects. Mol. Ther. 17, 725\u2013732 (2009).","journal-title":"Mol. Ther."},{"key":"7299_CR36","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","volume":"18","author":"Percie du Sert","year":"2020","unstructured":"Percie du Sert. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 18, e3000410. https:\/\/doi.org\/10.1371\/journal.pbio.3000410 (2020).","journal-title":"PLoS Biol."},{"key":"7299_CR37","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1038\/nprot.2013.135","volume":"8","author":"V Lambert","year":"2013","unstructured":"Lambert, V. et al. Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice. Nat. Protoc. 8, 2197\u20132211. https:\/\/doi.org\/10.1038\/nprot.2013.135 (2013).","journal-title":"Nat. Protoc."},{"key":"7299_CR38","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1167\/iovs.14-13897","volume":"55","author":"J Lee","year":"2014","unstructured":"Lee, J. et al. Angiopoietin-1 suppresses choroidal neovascularization and vascular leakage. Invest. Ophthalmol. Vis. Sci. 55, 2191\u20132199. https:\/\/doi.org\/10.1167\/iovs.14-13897 (2014).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"7299_CR39","doi-asserted-by":"publisher","first-page":"10551","DOI":"10.1074\/jbc.M110.209759","volume":"286","author":"S Sakami","year":"2011","unstructured":"Sakami, S. et al. Probing mechanisms of photoreceptor degeneration in a new mouse model of the common form of autosomal dominant retinitis pigmentosa due to P23H Opsin mutations. J. Biol. Chem. 286, 10551\u201310567. https:\/\/doi.org\/10.1074\/jbc.M110.209759 (2011).","journal-title":"J. Biol. Chem."},{"key":"7299_CR40","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1007\/s12035-014-8881-8","volume":"52","author":"WC Chiang","year":"2015","unstructured":"Chiang, W. C. et al. Robust endoplasmic reticulum-associated degradation of rhodopsin precedes retinal degeneration. Mol. Neurobiol. 52, 679\u2013695. https:\/\/doi.org\/10.1007\/s12035-014-8881-8 (2015).","journal-title":"Mol. Neurobiol."},{"key":"7299_CR41","doi-asserted-by":"publisher","first-page":"4902","DOI":"10.1038\/s41467-019-12780-8","volume":"10","author":"M Menon","year":"2019","unstructured":"Menon, M. et al. Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration. Nat. Commun. 10, 4902. https:\/\/doi.org\/10.1038\/s41467-019-12780-8 (2019).","journal-title":"Nat. Commun."},{"key":"7299_CR42","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/nchembio839","volume":"2","author":"D Bumcrot","year":"2006","unstructured":"Bumcrot, D., Manoharan, M., Koteliansky, V. & Sah, D. W. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat. Chem. Biol. 2, 711\u2013719 (2006).","journal-title":"Nat. Chem. Biol."},{"key":"7299_CR43","doi-asserted-by":"publisher","first-page":"3615","DOI":"10.1172\/JCI33483","volume":"117","author":"DR Corey","year":"2007","unstructured":"Corey, D. R. Chemical modification: the key to clinical application of RNA interference? J. Clin. Invest. 117, 3615\u20133622 (2007).","journal-title":"J. Clin. Invest."},{"key":"7299_CR44","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/S0092-8674(01)00547-5","volume":"107","author":"A Nyk\u00e4nen","year":"2001","unstructured":"Nyk\u00e4nen, A., Haley, B. & Zamore, P. D. ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107, 309\u2013321 (2001).","journal-title":"Cell"},{"key":"7299_CR45","doi-asserted-by":"publisher","unstructured":"Orozco, L. D. et al. Integration of eQTL and a single-cell atlas in the human eye identifies causal genes for age-related macular degeneration. Cell Rep. 30, 1246\u20131259 e1246. https:\/\/doi.org\/10.1016\/j.celrep.2019.12.082   (2020).","DOI":"10.1016\/j.celrep.2019.12.082"},{"key":"7299_CR46","doi-asserted-by":"publisher","first-page":"e3000365","DOI":"10.1371\/journal.pbio.3000365","volume":"17","author":"Y Hu","year":"2019","unstructured":"Hu, Y. et al. Dissecting the transcriptome landscape of the human fetal neural retina and retinal pigment epithelium by single-cell RNA-seq analysis. PLoS Biol. 17, e3000365. https:\/\/doi.org\/10.1371\/journal.pbio.3000365 (2019).","journal-title":"PLoS Biol."},{"key":"7299_CR47","doi-asserted-by":"publisher","first-page":"24100","DOI":"10.1073\/pnas.1914143116","volume":"116","author":"AP Voigt","year":"2019","unstructured":"Voigt, A. P. et al. Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration. Proc. Natl. Acad. Sci. U.S.A. 116, 24100\u201324107. https:\/\/doi.org\/10.1073\/pnas.1914143116 (2019).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"7299_CR48","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1038\/nbt1339","volume":"25","author":"C Wolfrum","year":"2007","unstructured":"Wolfrum, C. et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat. Biotechnol. 25, 1149\u20131157 (2007).","journal-title":"Nat. Biotechnol."},{"key":"7299_CR49","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1261\/rna.1901810","volume":"16","author":"Q Ge","year":"2010","unstructured":"Ge, Q. et al. Effects of chemical modification on the potency, serum stability, and immunostimulatory properties of short ShRNAs. RNA 16, 118\u2013130 (2010).","journal-title":"RNA"},{"key":"7299_CR50","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1007\/S10059-011-0160-1","volume":"32","author":"S Jo","year":"2011","unstructured":"Jo, S. et al. Selection and optimization of asymmetric SiRNA targeting the human c-MET gene. Mol. Cells. 32, 543\u2013548 (2011).","journal-title":"Mol. Cells"},{"key":"7299_CR51","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1042\/BJ20140407","volume":"461","author":"SW Hong","year":"2014","unstructured":"Hong, S. W. et al. Effect of the guide strand 3\u2032-end structure on the gene-silencing potency of asymmetric SiRNA. Biochem. J. 461, 427\u2013434 (2014).","journal-title":"Biochem. J."},{"key":"7299_CR52","first-page":"3278","volume":"34","author":"C Curcio","year":"1993","unstructured":"Curcio, C., Millican, C. L., Allen, K. & Kalina, R. Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest. Ophthalmol. Vis. Sci. 34, 3278\u20133296 (1993).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"7299_CR53","doi-asserted-by":"publisher","first-page":"3400","DOI":"10.1096\/fj.201600511R","volume":"30","author":"CC Ronquillo","year":"2016","unstructured":"Ronquillo, C. C. et al. Ciliopathy-associated IQCB1\/NPHP5 protein is required for mouse photoreceptor outer segment formation. FASEB J. 30, 3400 (2016).","journal-title":"FASEB J."},{"issue":"16","key":"7299_CR54","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1093\/hmg\/10.16.1619","volume":"10","author":"NB Haider","year":"2001","unstructured":"Haider, N. B., Naggert, J. & Nishina, P. M. Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7\/rd7 mice. Hum. Mol. Genet. 10 (16), 1619\u20131626 (2001).","journal-title":"Hum. Mol. Genet."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07299-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07299-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07299-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:58:07Z","timestamp":1757293087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-07299-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,26]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7299"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-07299-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,26]]},"assertion":[{"value":"21 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"H.J., T.H., M.Y., S.P., S.W.H., and D.K.L. are employees of OliX Pharmaceuticals Inc. H.C. serves as a consultant for OliX Pharmaceuticals Inc. A related patent application has been filed: PCT\/KR2021\/018460. The remaining authors - H.L., J.C., H.K.L., C.S., C.P., S.Y.L., J.L., and S.L. - declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27176"}}