{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T21:14:42Z","timestamp":1776201282738,"version":"3.50.1"},"reference-count":51,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy Methods & Clinical Development"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.omtm.2025.101625","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T19:11:32Z","timestamp":1762369892000},"page":"101625","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and efficacy of AAV8-aflibercept in treating choroidal neovascularization via single-cell RNA sequencing"],"prefix":"10.1016","volume":"33","author":[{"given":"Jiemei","family":"Shi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaicheng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinling","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-9292","authenticated-orcid":false,"given":"Chunhui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2025.101625_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.175586","article-title":"The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF","volume":"949","author":"Ghalehbandi","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.omtm.2025.101625_bib2","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21249752","article-title":"Associations between the Complement System and Choroidal Neovascularization in Wet Age-Related Macular Degeneration","volume":"21","author":"Jensen","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.omtm.2025.101625_bib3","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.18632\/oncotarget.14020","article-title":"Choroidal microvascular proliferation secondary to diabetes mellitus","volume":"8","author":"Hua","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.omtm.2025.101625_bib4","doi-asserted-by":"crossref","first-page":"17347","DOI":"10.18632\/oncotarget.14468","article-title":"Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-\u03baB signaling pathway in a rat model","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.omtm.2025.101625_bib5","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/s10792-024-03299-z","article-title":"Advancements and emerging trends in ophthalmic anti-VEGF therapy: a bibliometric analysis","volume":"44","author":"Deng","year":"2024","journal-title":"Int. Ophthalmol."},{"key":"10.1016\/j.omtm.2025.101625_bib6","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1007\/s00417-024-06531-9","article-title":"Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes","volume":"262","author":"Agostini","year":"2024","journal-title":"Graef Arch. Clin. Exp. Ophthalmol."},{"key":"10.1016\/j.omtm.2025.101625_bib7","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1038\/s41467-024-48221-4","article-title":"An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species","volume":"15","author":"Luo","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.omtm.2025.101625_bib8","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.preteyeres.2005.04.001","article-title":"Gene therapy in the cornea","volume":"24","author":"Mohan","year":"2005","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.omtm.2025.101625_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2024.101323","article-title":"Multiple gene therapy as a tool for regulating the expression of molecules involved in neovascular age-related macular degeneration","volume":"104","author":"Corydon","year":"2025","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.omtm.2025.101625_bib10","doi-asserted-by":"crossref","DOI":"10.3390\/genes15060720","article-title":"Gene Therapy for Non-Hereditary Retinal Disease: Age-Related Macular Degeneration, Diabetic Retinopathy, and Beyond","volume":"15","author":"Rowe","year":"2024","journal-title":"Genes (Basel)"},{"key":"10.1016\/j.omtm.2025.101625_bib11","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/S0140-6736(24)00310-6","article-title":"Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1\/2a dose-escalation study","volume":"403","author":"Campochiaro","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.omtm.2025.101625_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2023.102394","article-title":"Safety and efficacy of ixoberogene soroparvovec in neovascular age-related macular degeneration in the United States (OPTIC): a prospective, two-year, multicentre phase 1 study","volume":"67","author":"Khanani","year":"2024","journal-title":"eClinicalMedicine"},{"key":"10.1016\/j.omtm.2025.101625_bib13","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1001\/jamaophthalmol.2018.6902","article-title":"Immune Response and Intraocular Inflammation in Patients With Leber Hereditary Optic Neuropathy Treated With Intravitreal Injection of Recombinant Adeno-Associated Virus 2 Carrying the ND4 Gene: A Secondary Analysis of a Phase 1\/2 Clinical Trial","volume":"137","author":"Bouquet","year":"2019","journal-title":"JAMA Ophthalmol."},{"key":"10.1016\/j.omtm.2025.101625_bib14","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.975803","article-title":"Immunogenicity and toxicity of AAV gene therapy","volume":"13","author":"Ertl","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.omtm.2025.101625_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2024.101206","article-title":"A novel class of self-complementary AAV vectors with multiple advantages based on cceAAV lacking mutant ITR","volume":"32","author":"Zhang","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101625_bib16","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.ajo.2012.03.047","article-title":"Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans","volume":"154","author":"Krohne","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.omtm.2025.101625_bib17","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1097\/IAE.0000000000002566","article-title":"Pharmacokinetic Study of Intravitreal Aflibercept in Humans with Neovascular Age-Related Macular Degeneration","volume":"40","author":"Do","year":"2020","journal-title":"Retina"},{"key":"10.1016\/j.omtm.2025.101625_bib18","doi-asserted-by":"crossref","first-page":"939","DOI":"10.2147\/OPTH.S100168","article-title":"Impact of injection therapy on retinal patients with diabetic macular edema or retinal vein occlusion","volume":"10","author":"Sivaprasad","year":"2016","journal-title":"Clin. Ophthalmol."},{"key":"10.1016\/j.omtm.2025.101625_bib19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ophtha.2013.08.011","article-title":"Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies","volume":"121","author":"Schmidt-Erfurth","year":"2014","journal-title":"Ophthalmology"},{"key":"10.1016\/j.omtm.2025.101625_bib20","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.omtn.2019.01.012","article-title":"Suppression of Choroidal Neovascularization by AAV-Based Dual-Acting Antiangiogenic Gene Therapy","volume":"16","author":"Askou","year":"2019","journal-title":"Mol. Ther. Nucl. Acids"},{"key":"10.1016\/j.omtm.2025.101625_bib21","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.omtn.2022.02.019","article-title":"VEGFA-targeting miR-agshRNAs combine efficacy with specificity and safety for retinal gene therapy","volume":"28","author":"Alsing","year":"2022","journal-title":"Mol. Ther. Nucl. Acids"},{"key":"10.1016\/j.omtm.2025.101625_bib22","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1016\/j.ymthe.2023.09.019","article-title":"Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration","volume":"31","author":"Ke","year":"2023","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101625_bib23","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.omtm.2022.01.002","article-title":"Delivery of nVEGFi using AAV8 for the treatment of neovascular age-related macular degeneration","volume":"24","author":"She","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101625_bib24","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1089\/hum.2018.144","article-title":"Dosage Thresholds and Influence of Transgene Cassette in Adeno-Associated Virus-Related Toxicity","volume":"29","author":"Khabou","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101625_bib25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1167\/iovs.63.9.11","article-title":"Animal Models of Choroidal Neovascularization: A Systematic Review","volume":"63","author":"Fabian-Jessing","year":"2022","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.omtm.2025.101625_bib26","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.ophtha.2011.03.020","article-title":"The 1-year results of CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing","volume":"118","author":"Heier","year":"2011","journal-title":"Ophthalmology"},{"key":"10.1016\/j.omtm.2025.101625_bib27","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1089\/hum.2015.130","article-title":"Cone-Specific Promoters for Gene Therapy of Achromatopsia and Other Retinal Diseases","volume":"27","author":"Ye","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101625_bib28","doi-asserted-by":"crossref","first-page":"e0148874","DOI":"10.1371\/journal.pone.0148874","article-title":"AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy","volume":"11","author":"Dinculescu","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2025.101625_bib29","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.bbrc.2019.05.117","article-title":"Gene delivery to cone photoreceptors by subretinal injection of rAAV2\/6 in the mouse retina","volume":"515","author":"Hori","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.omtm.2025.101625_bib30","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1016\/j.ymthe.2017.08.018","article-title":"AAV8 Can Induce Innate and Adaptive Immune Response in the Primate Eye","volume":"25","author":"Reichel","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101625_bib31","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1073\/pnas.1821000116","article-title":"AAV cis-regulatory sequences are correlated with ocular toxicity","volume":"116","author":"Xiong","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2025.101625_bib32","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.molcel.2015.04.005","article-title":"The technology and biology of single-cell RNA sequencing","volume":"58","author":"Kolodziejczyk","year":"2015","journal-title":"Mol. Cell"},{"key":"10.1016\/j.omtm.2025.101625_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2020.100915","article-title":"Immune responses to retinal gene therapy using adeno-associated viral vectors - Implications for treatment success and safety","volume":"83","author":"Bucher","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.omtm.2025.101625_bib34","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.bcp.2009.04.029","article-title":"Inflammatory cytokines in vascular dysfunction and vascular disease","volume":"78","author":"Sprague","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.omtm.2025.101625_bib35","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1038\/cdd.2010.19","article-title":"TNF-alpha-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-X(L)","volume":"17","author":"Kim","year":"2010","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.omtm.2025.101625_bib36","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2022.1021207","article-title":"The role of Gadd45b in neurologic and neuropsychiatric disorders: An overview","volume":"15","author":"Shen","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.omtm.2025.101625_bib37","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1167\/iovs.12-10142","article-title":"TGF\u03b2 signaling induces expression of Gadd45b in retinal ganglion cells","volume":"54","author":"Liu","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.omtm.2025.101625_bib38","doi-asserted-by":"crossref","first-page":"e0170458","DOI":"10.1371\/journal.pone.0170458","article-title":"Transcriptome-wide co-expression analysis identifies LRRC2 as a novel mediator of mitochondrial and cardiac function","volume":"12","author":"McDermott-Roe","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2025.101625_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2022.155293","article-title":"Kdm6a deficiency in microglia\/macrophages epigenetically silences Lcn2 expression and reduces photoreceptor dysfunction in diabetic retinopathy","volume":"136","author":"Wen","year":"2022","journal-title":"Metabolism"},{"key":"10.1016\/j.omtm.2025.101625_bib40","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.7150\/thno.104752","article-title":"LCN2 deficiency mitigates the neuroinflammatory damage following acute glaucoma","volume":"15","author":"Hu","year":"2025","journal-title":"Theranostics"},{"key":"10.1016\/j.omtm.2025.101625_bib41","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s10020-025-01250-1","article-title":"Lipocalin-2-mediated ferroptosis as a target for protection against light-induced photoreceptor degeneration","volume":"31","author":"Tang","year":"2025","journal-title":"Mol. Med."},{"key":"10.1016\/j.omtm.2025.101625_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.mam.2022.101106","article-title":"Cathepsin S (CTSS) activity in health and disease - A treasure trove of untapped clinical potential","volume":"88","author":"Smyth","year":"2022","journal-title":"Mol. Aspects Med."},{"key":"10.1016\/j.omtm.2025.101625_bib43","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-29411-9","article-title":"Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sj\u00f6gren's Syndrome patients","volume":"8","author":"Edman","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omtm.2025.101625_bib44","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19113530","article-title":"Cathepsin S Alters the Expression of Pro-Inflammatory Cytokines and MMP-9, Partially through Protease-Activated Receptor-2, in Human Corneal Epithelial Cells","volume":"19","author":"Klinngam","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.omtm.2025.101625_bib45","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1111\/j.1582-4934.2010.01229.x","article-title":"Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis","volume":"15","author":"Haves-Zburof","year":"2011","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.omtm.2025.101625_bib46","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/ejhg.2011.151","article-title":"C1q enhances cone photoreceptor survival in a mouse model of autosomal recessive retinitis pigmentosa","volume":"20","author":"Humphries","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.omtm.2025.101625_bib47","doi-asserted-by":"crossref","first-page":"5792","DOI":"10.1167\/iovs.17-22473","article-title":"Superior Retinal Gene Transfer and Biodistribution Profile of Subretinal Versus Intravitreal Delivery of AAV8 in Nonhuman Primates","volume":"58","author":"Seitz","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.omtm.2025.101625_bib48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.omtm.2017.12.001","article-title":"Nonclinical Safety Evaluation of scAAV8-RLBP1 for Treatment of RLBP1 Retinitis Pigmentosa","volume":"8","author":"MacLachlan","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101625_bib49","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.omtm.2018.11.004","article-title":"Scalable Production of AAV Vectors in Orbitally Shaken HEK293 Cells","volume":"13","author":"Blessing","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101625_bib50","doi-asserted-by":"crossref","first-page":"e0132643","DOI":"10.1371\/journal.pone.0132643","article-title":"Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice","volume":"10","author":"Gong","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2025.101625_bib51","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1167\/iovs.17-23083","article-title":"Intravitreal Stanniocalcin-1 Enhances New Blood Vessel Growth in a Rat Model of Laser-Induced Choroidal Neovascularization","volume":"59","author":"Zhao","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."}],"container-title":["Molecular Therapy Methods & Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125002207?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125002207?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T20:30:55Z","timestamp":1776198655000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050125002207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S2329050125002207"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101625","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Safety and efficacy of AAV8-aflibercept in treating choroidal neovascularization via single-cell RNA sequencing","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101625","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}],"article-number":"101625"}}