{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:56:20Z","timestamp":1774317380223,"version":"3.50.1"},"reference-count":44,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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":[[2025,3]]},"DOI":"10.1016\/j.omtm.2025.101426","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:14:04Z","timestamp":1738628044000},"page":"101426","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cell-penetrating peptide-grafted AAV2 capsids for improved retinal delivery via intravitreal injection"],"prefix":"10.1016","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1551-9660","authenticated-orcid":false,"given":"Jiang-Hui","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengtian","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackson","family":"McGowan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-Yun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic J.","family":"Gessler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Punzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip W.L.","family":"Tai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangping","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2025.101426_bib1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.omtm.2025.101426_bib2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41392-024-01780-w","article-title":"Adeno-associated virus as a delivery vector for gene therapy of human diseases","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib3","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.1016\/j.ymthe.2024.10.017","article-title":"Recombinant Adeno-Associated Virus as a Delivery Platform for Ocular Gene Therapy: A Comprehensive Review","volume":"32","author":"Wang","year":"2024","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib4","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.ymthe.2020.11.029","article-title":"Clinical Perspective: Treating RPE65-Associated Retinal Dystrophy","volume":"29","author":"Maguire","year":"2021","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1167\/tvst.7.4.6","article-title":"Inherited Retinal Degenerations: Current Landscape and Knowledge Gaps","volume":"7","author":"Duncan","year":"2018","journal-title":"Transl. Vis. Sci. Technol."},{"key":"10.1016\/j.omtm.2025.101426_bib6","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","article-title":"Engineering adeno-associated virus vectors for gene therapy","volume":"21","author":"Li","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.omtm.2025.101426_bib7","doi-asserted-by":"crossref","first-page":"9878","DOI":"10.1128\/JVI.01568-16","article-title":"Heparan Sulfate Binding Promotes Accumulation of Intravitreally Delivered Adeno-associated Viral Vectors at the Retina for Enhanced Transduction but Weakly Influences Tropism","volume":"90","author":"Woodard","year":"2016","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.omtm.2025.101426_bib8","doi-asserted-by":"crossref","first-page":"189ra76","DOI":"10.1126\/scitranslmed.3005708","article-title":"In\u00a0vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous","volume":"5","author":"Dalkara","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.omtm.2025.101426_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2021.108545","article-title":"The internal limiting membrane: Roles in retinal development and implications for emerging ocular therapies","volume":"206","author":"Zhang","year":"2021","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.omtm.2025.101426_bib10","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s10867-008-9074-3","article-title":"Cell Penetrating Peptides: How Do They Do It?","volume":"33","author":"Herce","year":"2007","journal-title":"J.\u00a0Biol. Phys."},{"key":"10.1016\/j.omtm.2025.101426_bib11","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.3390\/cells12071071","article-title":"Ocular Delivery of Therapeutic Agents by Cell-Penetrating Peptides","volume":"12","author":"Nh\u00e0n","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.omtm.2025.101426_bib12","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1167\/iovs.16-20072","article-title":"Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides","volume":"58","author":"de Cogan","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.omtm.2025.101426_bib13","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1038\/s41551-022-00938-7","article-title":"Variants of the adeno-associated virus serotype 9 with enhanced penetration of the blood-brain barrier in rodents and primates","volume":"6","author":"Yao","year":"2022","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.omtm.2025.101426_bib14","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nbt.3440","article-title":"Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain","volume":"34","author":"Deverman","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtm.2025.101426_bib15","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/nn.4593","article-title":"Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems","volume":"20","author":"Chan","year":"2017","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.omtm.2025.101426_bib16","doi-asserted-by":"crossref","first-page":"D1098","DOI":"10.1093\/nar\/gkv1266","article-title":"CPPsite 2.0: a repository of experimentally validated cell-penetrating peptides","volume":"44","author":"Agrawal","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2025.101426_bib17","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.omtm.2020.12.006","article-title":"Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning","volume":"20","author":"Nonnenmacher","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101426_bib18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.omtm.2019.01.008","article-title":"Capsid Modifications for Targeting and Improving the Efficacy of AAV Vectors","volume":"12","author":"B\u00fcning","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101426_bib19","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/mt.2015.3","article-title":"High Capsid\u2013Genome Correlation Facilitates Creation of AAV Libraries for Directed Evolution","volume":"23","author":"Nonnenmacher","year":"2015","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib20","doi-asserted-by":"crossref","first-page":"20139","DOI":"10.1038\/mtm.2013.9","article-title":"Empty virions in AAV8 vector preparations reduce transduction efficiency and may cause total viral particle dose-limiting side effects","volume":"1","author":"Gao","year":"2014","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101426_bib21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1167\/tvst.10.4.3","article-title":"Inflammation in Viral Vector-Mediated Ocular Gene Therapy: A Review and Report From a Workshop Hosted by the Foundation Fighting Blindness, 9\/2020","volume":"10","author":"Chan","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"10.1016\/j.omtm.2025.101426_bib22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41434-024-00477-7","article-title":"The AAV2.7m8 capsid packages a higher degree of heterogeneous vector genomes than AAV2","volume":"31","author":"Cui","year":"2024","journal-title":"Gene Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fimmu.2014.00009","article-title":"Mapping the AAV Capsid Host Antibody Response toward the Development of Second Generation Gene Delivery Vectors","volume":"5","author":"Tseng","year":"2014","journal-title":"Front. Immunol."},{"key":"10.1016\/j.omtm.2025.101426_bib24","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1128\/JVI.00076-06","article-title":"Heparan sulfate proteoglycan binding properties of adeno-associated virus retargeting mutants and consequences for their in\u00a0vivo tropism","volume":"80","author":"Perabo","year":"2006","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.omtm.2025.101426_bib25","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.molmed.2018.06.006","article-title":"Seeing the Light after 25 Years of Retinal Gene Therapy","volume":"24","author":"Trapani","year":"2018","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.omtm.2025.101426_bib26","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/eye.2017.158","article-title":"Technique of retinal gene therapy: delivery of viral vector into the subretinal space","volume":"31","author":"Xue","year":"2017","journal-title":"Eye"},{"key":"10.1016\/j.omtm.2025.101426_bib27","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.virol.2008.08.027","article-title":"Tyrosine-phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression","volume":"381","author":"Zhong","year":"2008","journal-title":"Virology"},{"key":"10.1016\/j.omtm.2025.101426_bib28","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/mt.2010.234","article-title":"Novel Properties of Tyrosine-mutant AAV2 Vectors in the Mouse Retina","volume":"19","author":"Petrs-Silva","year":"2011","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib29","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.135112","article-title":"In vivo\u2013directed evolution of adeno-associated virus in the primate retina","volume":"5","author":"Byrne","year":"2020","journal-title":"JCI Insight"},{"key":"10.1016\/j.omtm.2025.101426_bib30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3762\/bjnano.11.10","article-title":"Internalization mechanisms of cell-penetrating peptides","volume":"11","author":"Ruseska","year":"2020","journal-title":"Beilstein J. Nanotechnol."},{"key":"10.1016\/j.omtm.2025.101426_bib31","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/mt.2012.40","article-title":"Do Cell-Penetrating Peptides Actually \u201cPenetrate\u201d Cellular Membranes?","volume":"20","author":"Palm-Apergi","year":"2012","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib32","doi-asserted-by":"crossref","first-page":"3594","DOI":"10.3390\/ph3123594","article-title":"Cell-Penetrating Penta-Peptides (CPP5s): Measurement of Cell Entry and Protein-Transduction Activity","volume":"3","author":"Gomez","year":"2010","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.omtm.2025.101426_bib33","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1089\/hum.2024.050","article-title":"Modulation of AAV9 Galactose Binding Yields Novel Gene Therapy Vectors and Predicts Cross-Species Differences in Glycan Avidity","volume":"35","author":"Hoffman","year":"2024","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib34","doi-asserted-by":"crossref","first-page":"113902","DOI":"10.1016\/j.celrep.2024.113902","article-title":"Capsid-mediated control of adeno-associated viral transcription determines host range","volume":"43","author":"Loeb","year":"2024","journal-title":"Cell Rep."},{"key":"10.1016\/j.omtm.2025.101426_bib35","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/s41565-023-01419-x","article-title":"Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain","volume":"18","author":"Chuapoco","year":"2023","journal-title":"Nat. Nanotechnol."},{"key":"10.1016\/j.omtm.2025.101426_bib36","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1128\/JVI.02093-13","article-title":"Adeno-Associated Virus Capsid Proteins May Play a Role in Transcription and Second-Strand Synthesis of Recombinant Genomes","volume":"88","author":"Salganik","year":"2014","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.omtm.2025.101426_bib37","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.ymthe.2020.03.007","article-title":"AAV Capsid-Promoter Interactions Determine CNS Cell-Selective Gene Expression In\u00a0Vivo","volume":"28","author":"Powell","year":"2020","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib38","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202013392","article-title":"Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders","volume":"13","author":"Pavlou","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.omtm.2025.101426_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0225206","article-title":"Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP.B capsids","volume":"14","author":"Huang","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2025.101426_bib40","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.ymthe.2019.02.013","article-title":"The GPI-Linked Protein LY6A Drives AAV-PHP.B Transport across the Blood-Brain Barrier","volume":"27","author":"Hordeaux","year":"2019","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib41","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.1016\/j.cell.2021.08.028","article-title":"Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species","volume":"184","author":"Tabebordbar","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2025.101426_bib42","doi-asserted-by":"crossref","first-page":"13094","DOI":"10.1073\/pnas.2000339117","article-title":"Altered photoreceptor metabolism in mouse causes late stage age-related macular degeneration-like pathologies","volume":"117","author":"Cheng","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2025.101426_bib43","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1089\/hum.2017.020","article-title":"Rod Outer Segment Development Influences AAV-Mediated Photoreceptor Transduction After Subretinal Injection","volume":"28","author":"Petit","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101426_bib44","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2023.101129","article-title":"Non-canonical amino acid incorporation into AAV5 capsid enhances lung transduction in mice","volume":"31","author":"Chang","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."}],"container-title":["Molecular Therapy Methods & Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S232905012500021X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S232905012500021X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:58:15Z","timestamp":1742518695000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S232905012500021X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["S232905012500021X"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101426","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cell-penetrating peptide-grafted AAV2 capsids for improved retinal delivery via intravitreal injection","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101426","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}],"article-number":"101426"}}