{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:18:35Z","timestamp":1791497915112,"version":"4.3.4"},"reference-count":85,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ophthalmic diseases, including inherited retinal dystrophies, age-related macular degeneration (AMD), and glaucomatous neuropathies, are often driven by the expression of pathogenic proteins or dysfunctional non-coding RNAs that are currently considered \u2018undruggable\u2019 with conventional small-molecule therapeutics. The emerging strategy of Ribonuclease-Targeting Chimeras (RIBOTACs) offers a revolutionary approach to address this therapeutic gap. RIBOTACs are heterobifunctional small molecules designed to bind a specific target RNA with one moiety and recruit a latent endogenous ribonuclease, such as RNase L, with the other, thereby catalyzing the RNA\u2019s degradation. This targeted degradation can potentially halt the production of mutant proteins, eliminate toxic gain-of-function RNAs, or modulate key regulatory pathways involved in angiogenesis, inflammation, and apoptosis\u2014core processes in many blinding diseases. This review explores the immense potential of applying RIBOTAC technology to ophthalmology, discussing prospective targets such as mutant alleles in retinitis pigmentosa, VEGF transcripts in neovascular AMD, and inflammatory mediators in uveitis. We will also address the unique challenges and opportunities for RIBOTAC development in the eye, including delivery strategies to overcome ocular barriers, the need for high specificity to avoid off-target RNA degradation, and the optimization of pharmacokinetic properties for intraocular administration. With continued innovation, RIBOTACs are poised to evolve into a robust therapeutic platform, expanding the druggable genome and enabling precise, durable treatments for a range of currently intractable ophthalmic conditions.<\/jats:p>","DOI":"10.3390\/ijms27031493","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:00:58Z","timestamp":1770109258000},"page":"1493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted RNA Degradation by RIBOTACs: A Novel Therapeutic Avenue for Ophthalmic Diseases"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-2585","authenticated-orcid":false,"given":"Dario","family":"Rusciano","sequence":"first","affiliation":[{"name":"Fidia Pharmaceuticals, Ophthalmology Research, Catania University, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1051-876X","authenticated-orcid":false,"given":"Alessandro","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Neurovisual Science Technology (NEST), 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3808-8944","authenticated-orcid":false,"given":"Jos\u00e9 Fernando","family":"Maya-Vetencourt","sequence":"additional","affiliation":[{"name":"Department of Biology, Physiology Institute, University of Pisa, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1111\/febs.14827","article-title":"Long non-coding RNAs in ocular diseases: New and potential therapeutic targets","volume":"286","author":"Zhang","year":"2019","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.7150\/thno.19646","article-title":"Decoding Noncoding RNAs: Role of MicroRNAs and Long Noncoding RNAs in Ocular Neovascularization","volume":"7","author":"Zhang","year":"2017","journal-title":"Theranostics"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sharma, A., and Singh, N.K. (2023). Long Non-Coding RNAs and Proliferative Retinal Diseases. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051454"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123092","DOI":"10.1016\/j.lfs.2024.123092","article-title":"Roles of noncoding RNAs in diabetic retinopathy: Mechanisms and therapeutic implications","volume":"357","author":"Xiao","year":"2024","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.18632\/aging.205656","article-title":"Identification of key lncRNAs in age-related macular degeneration through integrated bioinformatics and experimental validation","volume":"16","author":"Ji","year":"2024","journal-title":"Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3233\/NPM-230029","article-title":"The association of microRNAs in the development of retinopathy of prematurity","volume":"17","author":"Ovali","year":"2024","journal-title":"J. Neonatal-Perinat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"174035","DOI":"10.1016\/j.ejphar.2021.174035","article-title":"MicroRNA-126 inhibits pathological retinal neovascularization via suppressing vascular endothelial growth factor expression in a rat model of retinopathy of prematurity","volume":"900","author":"Fan","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, Y., Zhou, H., Huang, Q., Tan, W., Cai, Y., Wang, Z., Zou, J., Li, B., Yoshida, S., and Zhou, Y. (2022). Potential biomarkers for retinopathy of prematurity identified by circular RNA profiling in peripheral blood mononuclear cells. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.953812"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s42003-023-05064-x","article-title":"Circular RNA RSU1 promotes retinal vascular dysfunction by regulating miR-345-3p\/TAZ","volume":"6","author":"Zhang","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1080\/08820538.2021.1914116","article-title":"Antisense Oligonucleotide Therapy for Ophthalmic Conditions","volume":"36","author":"Ferenchak","year":"2021","journal-title":"Semin. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108482","DOI":"10.1016\/j.exer.2021.108482","article-title":"RNA therapeutics in ophthalmology\u2014Translation to clinical trials","volume":"205","author":"Gupta","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Collotta, D., Bertocchi, I., Chiapello, E., and Collino, M. (2023). Antisense oligonucleotides: A novel Frontier in pharmacological strategy. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1304342"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"241","DOI":"10.4062\/biomolther.2023.001","article-title":"Drug Discovery Perspectives of Antisense Oligonucleotides","volume":"31","author":"Kim","year":"2023","journal-title":"Biomol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1177\/193229680900300440","article-title":"Antisense oligonucleotide therapy in diabetic retinopathy","volume":"3","author":"Hnik","year":"2009","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1080\/17460441.2023.2224960","article-title":"Targeted Degradation of Structured RNAs via Ribonuclease-Targeting Chimeras (RiboTacs)","volume":"18","author":"Nandi","year":"2023","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Komachankandy, S., and Lee, Y. (2025). Targeted RNA Degradation as a Promising Therapeutic Strategy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110767"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.trecan.2025.08.011","article-title":"Fueling the revolution: RIBOTACs manipulating RNA decay","volume":"11","author":"Zhou","year":"2025","journal-title":"Trends Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13044","DOI":"10.1021\/jacs.1c02248","article-title":"Reprogramming of Protein-Targeted Small-Molecule Medicines to RNA by Ribonuclease Recruitment","volume":"143","author":"Zhang","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21096","DOI":"10.1021\/jacs.2c07217","article-title":"DNA-Encoded Library Screening To Inform Design of a Ribonuclease Targeting Chimera (RiboTAC)","volume":"144","author":"Meyer","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21525","DOI":"10.1021\/jacs.4c04717","article-title":"Transcriptome-Wide, Unbiased Profiling of Ribonuclease Targeting Chimeras","volume":"146","author":"Tong","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7167","DOI":"10.1039\/D0CS00560F","article-title":"Small molecule recognition of disease-relevant RNA structures","volume":"49","author":"Meyer","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7252","DOI":"10.1039\/D0CS00455C","article-title":"Design of small molecules targeting RNA structure from sequence","volume":"49","author":"Ursu","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/bs.mie.2023.06.006","article-title":"Methods for the study of ribonuclease targeting chimeras (RiboTACs)","volume":"692","author":"Springer","year":"2023","journal-title":"Methods Enzymol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/s41467-025-56691-3","article-title":"Stimulus-activated ribonuclease targeting chimeras for tumor microenvironment activated cancer therapy","volume":"16","author":"Zhang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15815","DOI":"10.1021\/jacs.4c02091","article-title":"G-Quadruplex mRNAs Silencing with Inducible Ribonuclease Targeting Chimera for Precision Tumor Therapy","volume":"146","author":"Zhang","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2306682120","DOI":"10.1073\/pnas.2306682120","article-title":"Decreasing the intrinsically disordered protein alpha-synuclein levels by targeting its structured mRNA with a ribonuclease-targeting chimera","volume":"121","author":"Tong","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/d41573-021-00189-2","article-title":"Degrading disease-causing RNA in ALS","volume":"20","author":"Cully","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e12715","DOI":"10.1002\/advs.202512715","article-title":"RNA G-Quadruplex RIBOTAC-Mediated Targeted Degradation of lncRNA TERRA","volume":"12","author":"Khaskia","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e41295","DOI":"10.1016\/j.heliyon.2024.e41295","article-title":"Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysis","volume":"11","author":"Khaskia","year":"2025","journal-title":"Heliyon"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s40942-025-00736-8","article-title":"RNA dysfunction in age-related macular degeneration: The role of U1 snRNP complex and neurodegenerative diseases","volume":"11","author":"Bottos","year":"2025","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"BSR20160589","DOI":"10.1042\/BSR20160589","article-title":"Plasma miR-21 expression: An indicator for the severity of Type 2 diabetes with diabetic retinopathy","volume":"37","author":"Jiang","year":"2017","journal-title":"Biosci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.3390\/genes16091060","article-title":"MicroRNA (miRNA) in the Pathogenesis of Diabetic Retinopathy: A Narrative Review","volume":"16","author":"Lampsas","year":"2025","journal-title":"Genes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.2337\/db16-1246","article-title":"Pathogenic Role of microRNA-21 in Diabetic Retinopathy Through Downregulation of PPARalpha","volume":"66","author":"Chen","year":"2017","journal-title":"Diabetes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.visres.2017.03.009","article-title":"miR-146a suppresses STAT3\/VEGF pathways and reduces apoptosis through IL-6 signaling in primary human retinal microvascular endothelial cells in high glucose conditions","volume":"139","author":"Ye","year":"2017","journal-title":"Vis. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, C.H., Huang, S., Britton, W.R., and Chen, J. (2020). MicroRNAs in Vascular Eye Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020649"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3109\/13816810.2013.848908","article-title":"C.57 C > T Mutation in MIR 184 is Responsible for Congenital Cataracts and Corneal Abnormalities in a Five-generation Family from Galicia, Spain","volume":"36","author":"Bykhovskaya","year":"2015","journal-title":"Ophthalmic Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7209","DOI":"10.1167\/iovs.15-17733","article-title":"MicroRNA-184 Regulates Corneal Lymphangiogenesis","volume":"56","author":"Grimaldo","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s12951-023-02019-6","article-title":"Exosomal miR-184 in the aqueous humor of patients with central serous chorioretinopathy: A potential diagnostic and prognostic biomarker","volume":"21","author":"Yang","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_39","first-page":"101562","article-title":"Rare variants in MIR184 are a novel genetic cause of Fuchs endothelial corneal dystrophy","volume":"27","author":"Sadan","year":"2025","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2337\/db20-0375","article-title":"Long Noncoding RNA MALAT1 and Regulation of the Antioxidant Defense System in Diabetic Retinopathy","volume":"70","author":"Radhakrishnan","year":"2021","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108984","DOI":"10.1016\/j.exer.2022.108984","article-title":"LncRNA MALAT1 aggravates the retinal angiogenesis via miR-320a\/HIF-1alpha axis in diabetic retinopathy","volume":"218","author":"Chen","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13578-024-01217-5","article-title":"The role of long noncoding RNAs in ocular angiogenesis and vascular oculopathy","volume":"14","author":"Gandhi","year":"2024","journal-title":"Cell Biosci."},{"key":"ref_43","first-page":"913","article-title":"Long noncoding RNA MALAT1 acts as a competing endogenous RNA to regulate Amadori-glycated albumin-induced MCP-1 expression in retinal microglia by a microRNA-124-dependent mechanism","volume":"67","author":"Dong","year":"2018","journal-title":"Inflamm. Res. Off. J. Eur. Histamine Res. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"BSR20181469","DOI":"10.1042\/BSR20181469","article-title":"LncRNA-MALAT1 promotes neovascularization in diabetic retinopathy through regulating miR-125b\/VE-cadherin axis","volume":"39","author":"Liu","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"108585","DOI":"10.1016\/j.exer.2021.108585","article-title":"Knockdown of Malat1 alleviates high-glucose-induced angiogenesis through regulating miR-205-5p\/VEGF-A axis","volume":"207","author":"Tan","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1080\/08916934.2021.1969551","article-title":"LncRNA XIST restrains the activation of Muller cells and inflammation in diabetic retinopathy via stabilizing SIRT1","volume":"54","author":"Zhang","year":"2021","journal-title":"Autoimmunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e230097","DOI":"10.20945\/2359-4292-2023-0097","article-title":"LncRNA XIST promotes neovascularization in diabetic retinopathy by regulating miR-101-3p\/VEGFA","volume":"68","author":"Fu","year":"2024","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1167\/tvst.13.7.7","article-title":"Lipid Nanoparticle-Mediated Delivery of mRNA Into the Mouse and Human Retina and Other Ocular Tissues","volume":"13","author":"Chambers","year":"2024","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gugleva, V., and Andonova, V. (2023). Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030474"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Baig, M.S., Karade, S.K., Ahmad, A., Khan, M.A., Haque, A., Webster, T.J., Faiyazuddin, M., and Al-Qahtani, N.H. (2024). Lipid-based nanoparticles: Innovations in ocular drug delivery. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1421959"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e202515064","DOI":"10.1002\/anie.202515064","article-title":"Bioorthogonal RNase L Recruitment Enables Targeted Inducible Degradation of SARS-CoV-2 RNA","volume":"64","author":"Xiong","year":"2025","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12974-023-02804-y","article-title":"The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage","volume":"20","author":"Zhu","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e00205","DOI":"10.1128\/JVI.00205-20","article-title":"RNase L Amplifies Interferon Signaling by Inducing Protein Kinase R-Mediated Antiviral Stress Granules","volume":"94","author":"Manivannan","year":"2020","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ramnani, B., Devale, T., Manivannan, P., Haridas, A., and Malathi, K. (2024). DHX15 and Rig-I Coordinate Apoptosis and Innate Immune Signaling by Antiviral RNase L. Viruses, 16.","DOI":"10.3390\/v16121913"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/nature06042","article-title":"Small self-RNA generated by RNase L amplifies antiviral innate immunity","volume":"448","author":"Malathi","year":"2007","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1878","DOI":"10.1002\/wrna.1878","article-title":"The Unusual Role of Ribonuclease L in Innate Immunity","volume":"15","author":"Karasik","year":"2024","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.chom.2015.02.010","article-title":"RNase L activates the NLRP3 inflammasome during viral infections","volume":"17","author":"Chakrabarti","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15916","DOI":"10.1073\/pnas.1513034112","article-title":"Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome","volume":"112","author":"Rath","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gaglia, M.M., Rycroft, C.H., and Glaunsinger, B.A. (2015). Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005305"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Won, J.I., Shin, J., Park, S.Y., Yoon, J., and Jeong, D.H. (2020). Global Analysis of the Human RNA Degradome Reveals Widespread Decapped and Endonucleolytic Cleaved Transcripts. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186452"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e149","DOI":"10.1038\/mtna.2013.72","article-title":"A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent","volume":"3","author":"Pedersen","year":"2014","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/nar\/gkab1273","article-title":"\u201cBind, cleave and leave\u201d: Multiple turnover catalysis of RNA cleavage by bulge-loop inducing supramolecular conjugates","volume":"50","author":"Amirloo","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"113589","DOI":"10.1016\/j.biopha.2022.113589","article-title":"Small-molecule screening of ribonuclease L binders for RNA degradation","volume":"154","author":"Borgelt","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ejpb.2015.04.033","article-title":"Evaluation of protein drug stability with vitreous humor in a novel ex-vivo intraocular model","volume":"95","author":"Patel","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113823","DOI":"10.1016\/j.jconrel.2025.113823","article-title":"Novel in vitro model for intravitreal drug dissolution and release studies of small molecules and their long-acting formulations","volume":"383","author":"Sorsa","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1016\/j.bpj.2015.10.002","article-title":"Diffusion Regulation in the Vitreous Humor","volume":"109","author":"Kasdorf","year":"2015","journal-title":"Biophys. J."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Rimpela, A.K., Kiiski, I., Deng, F., Kidron, H., and Urtti, A. (2018). Pharmacokinetic Simulations of Intravitreal Biologicals: Aspects of Drug Delivery to the Posterior and Anterior Segments. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11010009"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.jconrel.2023.09.021","article-title":"Experimental and mathematical approaches for drug delivery for the treatment of wet age-related macular degeneration","volume":"363","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Jang, M., Kang, M., Lee, E., and Shin, D. (2024). Ocular and Plasma Pharmacokinetics of Enavogliflozin Ophthalmic Solution in Preclinical Species. Pharmaceuticals, 17.","DOI":"10.3390\/ph17010111"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1167\/tvst.7.4.21","article-title":"A Controlled Release System for Long-Acting Intravitreal Delivery of Small Molecules","volume":"7","author":"Machinaga","year":"2018","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Junnuthula, V., Sadeghi Boroujeni, A., Cao, S., Tavakoli, S., Ridolfo, R., Toropainen, E., Ruponen, M., van Hest, J.C.M., and Urtti, A. (2021). Intravitreal Polymeric Nanocarriers with Long Ocular Retention and Targeted Delivery to the Retina and Optic Nerve Head Region. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040445"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1016\/j.drudis.2019.05.031","article-title":"Recent advances in intraocular sustained-release drug delivery devices","volume":"24","author":"Cao","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liu, L.C., Chen, Y.H., and Lu, D.W. (2023). Overview of Recent Advances in Nano-Based Ocular Drug Delivery. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015352"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Cubillos, S., and Kazlauskas, A. (2024). Manifestation of Pathology in Animal Models of Diabetic Retinopathy Is Delayed from the Onset of Diabetes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031610"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.21037\/atm-20-6737","article-title":"Animal models of diabetic retinopathy","volume":"9","author":"Quiroz","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_76","unstructured":"Food and Drug Administration (2024). Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics: Guidance for Industry, Food and Drug Administration."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1208\/s12248-022-00741-x","article-title":"Considerations in the Immunogenicity Assessment Strategy for Oligonucleotide Therapeutics (ONTs)","volume":"24","author":"Bano","year":"2022","journal-title":"AAPS J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"101242","DOI":"10.1016\/j.omtm.2024.101242","article-title":"Subretinal AAV delivery of RNAi-therapeutics targeting VEGFA reduces choroidal neovascularization in a large animal model","volume":"32","author":"Haldrup","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1007\/s40618-025-02680-8","article-title":"Potential diagnostic value of microRNAs in vascular complications of diabetes: A systematic review and meta-analysis","volume":"48","author":"Wang","year":"2025","journal-title":"J. Endocrinol. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"ElShelmani, H., Brennan, I., Kelly, D.J., and Keegan, D. (2021). Differential Circulating MicroRNA Expression in Age-Related Macular Degeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212321"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10146","DOI":"10.1039\/D3RA08475B","article-title":"In situ imaging of mRNA transcripts based on split-aptamer and split protein in living cells","volume":"14","author":"Peng","year":"2024","journal-title":"RSC Adv."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"101110","DOI":"10.1016\/j.preteyeres.2022.101110","article-title":"RNA-targeting strategies as a platform for ocular gene therapy","volume":"92","author":"Kumar","year":"2023","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"0041","DOI":"10.34133\/bdr.0041","article-title":"CRISPR-Cas13: Pioneering RNA Editing for Nucleic Acid Therapeutics","volume":"6","author":"Zhu","year":"2024","journal-title":"BioDesign Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e2408345121","DOI":"10.1073\/pnas.2408345121","article-title":"Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina","volume":"121","author":"Kumar","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Bot, J.F., Zhao, Z., Li, M., Kammeron, D., Shang, P., and Geijsen, N. (2026). Temporal dynamics of collateral RNA cleavage by LbuCas13a in human cells. Commun. Biol.","DOI":"10.1038\/s42003-026-09511-3"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1493\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:02:45Z","timestamp":1770109365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":85,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031493"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031493","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]}}}