{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:22:26Z","timestamp":1792167746423,"version":"4.4.0"},"reference-count":204,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T00:00:00Z","timestamp":1659225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation Asile des Aveugles","award":["."],"award-info":[{"award-number":["."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>This review offers the basics of lentiviral vector technologies, their advantages and pitfalls, and an overview of their use in the field of ophthalmology. First, the description of the global challenges encountered to develop safe and efficient lentiviral recombinant vectors for clinical application is provided. The risks and the measures taken to minimize secondary effects as well as new strategies using these vectors are also discussed. This review then focuses on lentiviral vectors specifically designed for ocular therapy and goes over preclinical and clinical studies describing their safety and efficacy. A therapeutic approach using lentiviral vector-mediated gene therapy is currently being developed for many ocular diseases, e.g., aged-related macular degeneration, retinopathy of prematurity, inherited retinal dystrophies (Leber congenital amaurosis type 2, Stargardt disease, Usher syndrome), glaucoma, and corneal fibrosis or engraftment rejection. In summary, this review shows how lentiviral vectors offer an interesting alternative for gene therapy in all ocular compartments.<\/jats:p>","DOI":"10.3390\/pharmaceutics14081605","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T04:04:00Z","timestamp":1659326640000},"page":"1605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Lentiviral Vectors for Ocular Gene Therapy"],"prefix":"10.3390","volume":"14","author":[{"given":"Yvan","family":"Arsenijevic","sequence":"first","affiliation":[{"name":"Unit Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-4489","authenticated-orcid":false,"given":"Adeline","family":"Berger","sequence":"additional","affiliation":[{"name":"Group Epigenetics of ocular diseases, Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Udry","sequence":"additional","affiliation":[{"name":"Unit Retinal Degeneration and Regeneration, Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1006-9733","authenticated-orcid":false,"given":"Corinne","family":"Kostic","sequence":"additional","affiliation":[{"name":"Group for Retinal Disorder Research, Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/365666a0","article-title":"A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells","volume":"365","author":"Bukrinsky","year":"1993","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1089\/hum.2011.058","article-title":"Lentiviral vectors: Their molecular design, safety, and use in laboratory and preclinical research","volume":"22","author":"Dropulic","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0092-8674(00)80828-4","article-title":"HIV-1 genome nuclear import is mediated by a central DNA flap","volume":"101","author":"Zennou","year":"2000","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.4049\/jimmunol.141.12.4181","article-title":"Characterization of GP120 binding to CD4 and an assay that measures ability of sera to inhibit this binding","volume":"141","author":"Schnittman","year":"1988","journal-title":"J. Immunol."},{"key":"ref_5","first-page":"536","article-title":"Human immunodeficiency viruses: Neutralization and receptors","volume":"1","author":"Weiss","year":"1988","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0958-1669(98)80029-3","article-title":"Lentiviruses as gene transfer agents for delivery to non-dividing cells","volume":"9","author":"Naldini","year":"1998","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.272.5259.263","article-title":"In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector","volume":"272","author":"Naldini","year":"1996","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0091-679X(08)60600-7","article-title":"Generation of high-titer pseudotyped retroviral vectors with very broad host range","volume":"43 Pt A","author":"Yee","year":"1994","journal-title":"Methods Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1089\/hum.2005.16.17","article-title":"Regulatory considerations for novel gene therapy products: A review of the process leading to the first clinical lentiviral vector","volume":"16","author":"Manilla","year":"2005","journal-title":"Hum. Gene Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.biochem.67.1.1","article-title":"HIV-1: Fifteen proteins and an RNA","volume":"67","author":"Frankel","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s12551-021-00922-6","article-title":"Insights into HIV uncoating from single-particle imaging techniques","volume":"14","author":"Zhang","year":"2022","journal-title":"Biophys. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1128\/MMBR.63.4.836-843.1999","article-title":"Retroviral DNA integration","volume":"63","author":"Hindmarsh","year":"1999","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"23213","DOI":"10.1074\/jbc.R100027200","article-title":"HIV integrase, a brief overview from chemistry to therapeutics","volume":"276","author":"Craigie","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2174\/156652308786848021","article-title":"Mechanisms governing lentivirus integration site selection","volume":"8","author":"Ciuffi","year":"2008","journal-title":"Curr. Gene Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17841","DOI":"10.1074\/jbc.M411681200","article-title":"The interaction of LEDGF\/p75 with integrase is lentivirus-specific and promotes DNA binding","volume":"280","author":"Busschots","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Engelman, A., and Cherepanov, P. (2008). The lentiviral integrase binding protein LEDGF\/p75 and HIV-1 replication. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000046"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1038\/nm1329","article-title":"A role for LEDGF\/p75 in targeting HIV DNA integration","volume":"11","author":"Ciuffi","year":"2005","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7087","DOI":"10.1128\/JVI.73.8.7087-7092.1999","article-title":"Interaction of human immunodeficiency virus-derived vectors with wild-type virus in transduced cells","volume":"73","author":"Bukovsky","year":"1999","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1172\/JCI61852","article-title":"Lentiviral vector integration in the human genome induces alternative splicing and generates aberrant transcripts","volume":"122","author":"Moiani","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nature09328","article-title":"Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia","volume":"467","author":"Payen","year":"2010","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.ymthe.2019.12.009","article-title":"Retroviral Insertional Mutagenesis in Humans: Evidence for Four Genetic Mechanisms Promoting Expansion of Cell Clones","volume":"28","author":"Bushman","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nm1393","article-title":"Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1","volume":"12","author":"Ott","year":"2006","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1126\/science.288.5466.669","article-title":"Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease","volume":"288","author":"Gross","year":"2000","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1126\/science.1088547","article-title":"LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1","volume":"302","author":"Schmidt","year":"2003","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1038\/nm.2057","article-title":"Comprehensive genomic access to vector integration in clinical gene therapy","volume":"15","author":"Gabriel","year":"2009","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.omtm.2022.01.009","article-title":"Rapid, accurate mapping of transgene integration in viable rhesus macaque embryos using enhanced-specificity tagmentation-assisted PCR","volume":"24","author":"Ryu","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Corre, G., Seye, A., Frin, S., Ferrand, M., Winkler, K., Luc, C., Dorange, F., Rocca, C.J., and Galy, A. (2022). Lentiviral standards to determine the sensitivity of assays that quantify lentiviral vector copy numbers and genomic insertion sites in cells. Gene Ther.","DOI":"10.1038\/s41434-022-00315-8"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/gt.2011.194","article-title":"Absence of ocular malignant transformation after sub-retinal delivery of rAAV2\/2 or integrating lentiviral vectors in p53-deficient mice","volume":"19","author":"Balaggan","year":"2012","journal-title":"Gene Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1172\/JCI35700","article-title":"Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1","volume":"118","author":"Garrigue","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41551-020-00656-y","article-title":"Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa-targeting guide RNA prevents wet age-related macular degeneration in mice","volume":"5","author":"Ling","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1128\/JVI.72.12.9873-9880.1998","article-title":"Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery","volume":"72","author":"Zufferey","year":"1998","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1006\/viro.1999.9850","article-title":"Self-inactivating lentiviral vectors with U3 and U5 modifications","volume":"261","author":"Iwakuma","year":"1999","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10319","DOI":"10.1073\/pnas.94.19.10319","article-title":"Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector","volume":"94","author":"Miyoshi","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1073\/pnas.83.10.3194","article-title":"Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells","volume":"83","author":"Yu","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1128\/JVI.73.4.2886-2892.1999","article-title":"Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors","volume":"73","author":"Zufferey","year":"1999","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1089\/hum.2012.008","article-title":"Safety and biodistribution of an equine infectious anemia virus-based gene therapy, RetinoStat(\u00ae), for age-related macular degeneration","volume":"23","author":"Binley","year":"2012","journal-title":"Hum. Gene Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Verrier, J.D., Madorsky, I., Coggin, W.E., Geesey, M., Hochman, M., Walling, E., Daroszewski, D., Eccles, K.S., Ludlow, R., and Semple-Rowland, S.L. (2011). Bicistronic lentiviruses containing a viral 2A cleavage sequence reliably co-express two proteins and restore vision to an animal model of LCA1. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020553"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/jgm.845","article-title":"Stable and efficient intraocular gene transfer using pseudotyped EIAV lentiviral vectors","volume":"8","author":"Balaggan","year":"2006","journal-title":"J. Gene Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/mt.2010.278","article-title":"Replication-competent lentivirus analysis of clinical grade vector products","volume":"19","author":"Cornetta","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1089\/hum.2015.166","article-title":"\u201cRCL-Pooling Assay\u201d: A Simplified Method for the Detection of Replication-Competent Lentiviruses in Vector Batches Using Sequential Pooling","volume":"27","author":"Corre","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15017","DOI":"10.1038\/mtm.2015.17","article-title":"Development of a replication-competent lentivirus assay for dendritic cell-targeting lentiviral vectors","volume":"2","author":"Farley","year":"2015","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.ymthe.2003.08.003","article-title":"Certification assays for HIV-1-based vectors: Frequent passage of gag sequences without evidence of replication-competent viruses","volume":"8","author":"Sastry","year":"2003","journal-title":"Mol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.omtm.2017.09.001","article-title":"Detection of Replication Competent Lentivirus Using a qPCR Assay for VSV-G","volume":"8","author":"Skrdlant","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1089\/biores.2013.0037","article-title":"A Rev-Independent gag\/pol Eliminates Detectable psi-gag Recombination in Lentiviral Vectors","volume":"2","author":"Tareen","year":"2013","journal-title":"Biores. Open Access"},{"key":"ref_45","first-page":"449","article-title":"Production of trans-lentiviral vector with predictable safety","volume":"76","author":"Kappes","year":"2003","journal-title":"Methods Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1006\/mthe.2000.0095","article-title":"Development of a novel trans-lentiviral vector that affords predictable safety","volume":"2","author":"Wu","year":"2000","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.omtm.2018.08.006","article-title":"Screening Clinical Cell Products for Replication Competent Retrovirus: The National Gene Vector Biorepository Experience","volume":"10","author":"Cornetta","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1016\/j.ymthe.2017.04.028","article-title":"Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy","volume":"25","author":"Vink","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.omtm.2017.04.002","article-title":"Integrase-Deficient Lentiviral Vector as an All-in-One Platform for Highly Efficient CRISPR\/Cas9-Mediated Gene Editing","volume":"5","author":"Ortinski","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/mt.2009.122","article-title":"Integration-deficient lentiviral vectors: A slow coming of age","volume":"17","author":"Wanisch","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jconrel.2017.12.029","article-title":"High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors","volume":"273","author":"Ahmed","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/nm1365","article-title":"Effective gene therapy with nonintegrating lentiviral vectors","volume":"12","author":"Balaggan","year":"2006","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9011","DOI":"10.1128\/JVI.73.11.9011-9020.1999","article-title":"Structure-based mutagenesis of the human immunodeficiency virus type 1 DNA attachment site: Effects on integration and cDNA synthesis","volume":"73","author":"Brown","year":"1999","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/biomedicines2010014","article-title":"Design and Potential of Non-Integrating Lentiviral Vectors","volume":"2","author":"Shaw","year":"2014","journal-title":"Biomedicines"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1742-4690-10-21","article-title":"DNA damage enhances integration of HIV-1 into macrophages by overcoming integrase inhibition","volume":"10","author":"Koyama","year":"2013","journal-title":"Retrovirology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.ymthe.2006.01.008","article-title":"Transient gene expression by nonintegrating lentiviral vectors","volume":"13","author":"Nightingale","year":"2006","journal-title":"Mol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/nm0398-354","article-title":"Efficient transduction of nondividing human cells by feline immunodeficiency virus lentiviral vectors","volume":"4","author":"Poeschla","year":"1998","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/bit.21467","article-title":"Production of lentiviral vectors by large-scale transient transfection of suspension cultures and affinity chromatography purification","volume":"98","author":"Segura","year":"2007","journal-title":"Biotechnol. Bioeng."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5271","DOI":"10.1038\/s41598-018-23593-y","article-title":"LentiPro26: Novel stable cell lines for constitutive lentiviral vector production","volume":"8","author":"Tomas","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5665","DOI":"10.1046\/j.1432-1327.2000.01645.x","article-title":"Episomal vectors for gene expression in mammalian cells","volume":"267","author":"Vanhoenacker","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1089\/hum.2010.060","article-title":"Large-scale manufacture and characterization of a lentiviral vector produced for clinical ex vivo gene therapy application","volume":"22","author":"Merten","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1517\/14712598.2013.779249","article-title":"New developments in lentiviral vector design, production and purification","volume":"13","author":"Segura","year":"2013","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/gt.2010.162","article-title":"Production and purification of lentiviral vectors generated in 293T suspension cells with baculoviral vectors","volume":"18","author":"Lesch","year":"2011","journal-title":"Gene Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/gt.2008.76","article-title":"Generation of lentivirus vectors using recombinant baculoviruses","volume":"15","author":"Lesch","year":"2008","journal-title":"Gene Ther."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Martinez-Molina, E., Chocarro-Wrona, C., Martinez-Moreno, D., Marchal, J.A., and Boulaiz, H. (2020). Large-Scale Production of Lentiviral Vectors: Current Perspectives and Challenges. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111051"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108202","DOI":"10.1016\/j.bej.2021.108202","article-title":"Gene therapy process change evaluation framework: Transient transfection and stable producer cell line comparison","volume":"176","author":"Comisel","year":"2021","journal-title":"Biochem. Eng. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jviromet.2011.06.019","article-title":"Highly efficient large-scale lentiviral vector concentration by tandem tangential flow filtration","volume":"177","author":"Cooper","year":"2011","journal-title":"J. Virol. Methods"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Zimmermann, K., Scheibe, O., Kocourek, A., Muelich, J., Jurkiewicz, E., and Pfeifer, A. (2011). Highly efficient concentration of lenti- and retroviral vector preparations by membrane adsorbers and ultrafiltration. BMC Biotechnol., 11.","DOI":"10.1186\/1472-6750-11-55"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/bit.20301","article-title":"A novel purification strategy for retrovirus gene therapy vectors using heparin affinity chromatography","volume":"90","author":"Segura","year":"2005","journal-title":"Biotechnol. Bioeng."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"89","DOI":"10.12665\/J25.Dropulic","article-title":"Large-scale purification of a lentiviral vector by size exclusion chromatography or Mustang Q ion exchange capsule","volume":"2","author":"Dropulic","year":"2003","journal-title":"Bioprocess. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1002\/jssc.202100937","article-title":"Clinical grade lentiviral vector purification and quality control requirements","volume":"45","author":"Shi","year":"2022","journal-title":"J. Sep. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1089\/hum.2008.086","article-title":"Prolonged transgene expression with lentiviral vectors in the aqueous humor outflow pathway of nonhuman primates","volume":"20","author":"Barraza","year":"2009","journal-title":"Hum. Gene Ther."},{"key":"ref_73","first-page":"118","article-title":"Production, harvest, and concentration of feline immunodeficiency virus-based lentiviral vector from cells grown in CF10 or CF2 devices","volume":"2012","author":"Saenz","year":"2012","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_74","first-page":"40","article-title":"Evaluation of tolerance to lentiviral LV-RPE65 gene therapy vector after subretinal delivery in non-human primates","volume":"188","author":"Matet","year":"2017","journal-title":"Transl. Res. J. Lab. Clin. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1089\/hum.2009.009","article-title":"Stable retinal gene expression in nonhuman primates via subretinal injection of SIVagm-based lentiviral vectors","volume":"20","author":"Ikeda","year":"2009","journal-title":"Hum. Gene Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1167\/iovs.13-11871","article-title":"Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: Safety and biodistribution of StarGen for Stargardt disease","volume":"54","author":"Binley","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Zallocchi, M., Binley, K., Lad, Y., Ellis, S., Widdowson, P., Iqball, S., Scripps, V., Kelleher, M., Loader, J., and Miskin, J. (2014). EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: Development of UshStat. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094272"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/sj.gt.3302666","article-title":"A replication competent lentivirus (RCL) assay for equine infectious anaemia virus (EIAV)-based lentiviral vectors","volume":"13","author":"Miskin","year":"2006","journal-title":"Gene Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/jgm.1257","article-title":"Synergistic neuroprotective effect via simian lentiviral vector-mediated simultaneous gene transfer of human pigment epithelium-derived factor and human fibroblast growth factor-2 in rodent models of retinitis pigmentosa","volume":"10","author":"Miyazaki","year":"2008","journal-title":"J. Gene Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1038\/sj.gt.3302028","article-title":"Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats","volume":"10","author":"Miyazaki","year":"2003","journal-title":"Gene Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1089\/hum.2009.048","article-title":"Acute toxicity study of a simian immunodeficiency virus-based lentiviral vector for retinal gene transfer in nonhuman primates","volume":"20","author":"Ikeda","year":"2009","journal-title":"Hum. Gene Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.1167\/iovs.18-24978","article-title":"Effects of Lentivirus-Mediated C3 Expression on Trabecular Meshwork Cells and Intraocular Pressure","volume":"59","author":"Tan","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.ymthe.2019.04.021","article-title":"Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys","volume":"27","author":"Tan","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/sj.mt.6300318","article-title":"Durable, safe, multi-gene lentiviral vector expression in feline trabecular meshwork","volume":"16","author":"Khare","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/s41467-022-28762-2","article-title":"A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders","volume":"13","author":"Tucci","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1182\/blood-2013-11-540641","article-title":"Mystery solved: VSV-G-LVs do not allow efficient gene transfer into unstimulated T cells, B cells, and HSCs because they lack the LDL receptor","volume":"123","author":"Amirache","year":"2014","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7306","DOI":"10.1073\/pnas.1214441110","article-title":"LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus","volume":"110","author":"Finkelshtein","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/s41467-018-03432-4","article-title":"Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein","volume":"9","author":"Nikolic","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/ng1197-314","article-title":"Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors","volume":"17","author":"Kafri","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/exnr.1999.7178","article-title":"Lentiviral gene transfer to the nonhuman primate brain","volume":"160","author":"Kordower","year":"1999","journal-title":"Exp. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"11382","DOI":"10.1073\/pnas.93.21.11382","article-title":"Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector","volume":"93","author":"Naldini","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"10778","DOI":"10.1128\/JVI.74.22.10778-10784.2000","article-title":"Lentivirus vector gene expression during ES cell-derived hematopoietic development in vitro","volume":"74","author":"Hamaguchi","year":"2000","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/35017565","article-title":"Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin","volume":"406","author":"May","year":"2000","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1073\/pnas.251682798","article-title":"Transgenesis by lentiviral vectors: Lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos","volume":"99","author":"Pfeifer","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/sj.gt.3301948","article-title":"Activity analysis of housekeeping promoters using self-inactivating lentiviral vector delivery into the mouse retina","volume":"10","author":"Kostic","year":"2003","journal-title":"Gene Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1089\/104303403321070801","article-title":"Delivery of Ciliary Neurotrophic Factor via Lentiviral-Mediated Transfer Protects Axotomized Retinal Ganglion Cells for an Extended Period of Time","volume":"14","author":"Kostic","year":"2003","journal-title":"Hum.Gene Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/gt.2009.41","article-title":"Efficient lentiviral gene transfer into corneal stroma cells using a femtosecond laser","volume":"16","author":"Bemelmans","year":"2009","journal-title":"Gene Ther."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Calame, M., Cachafeiro, M., Philippe, S., Schouwey, K., Tekaya, M., Wanner, D., Sarkis, C., Kostic, C., and Arsenijevic, Y. (2011). Retinal degeneration progression changes lentiviral vector cell targeting in the retina. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023782"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1167\/iovs.05-1570","article-title":"Targeted transgene expression in muller glia of normal and diseased retinas using lentiviral vectors","volume":"48","author":"Greenberg","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1089\/hum.2013.009","article-title":"Vesicular stomatitis virus glycoprotein- and Venezuelan equine encephalitis virus-derived glycoprotein-pseudotyped lentivirus vectors differentially transduce corneal endothelium, trabecular meshwork, and human photoreceptors","volume":"25","author":"Lipinski","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1089\/10430340152677449","article-title":"Genetic modification of human trabecular meshwork with lentiviral vectors","volume":"12","author":"Loewen","year":"2001","journal-title":"Hum. Gene Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1167\/iovs.04-0366","article-title":"Long-term, targeted genetic modification of the aqueous humor outflow tract coupled with noninvasive imaging of gene expression in vivo","volume":"45","author":"Loewen","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1128\/JVI.78.2.912-921.2004","article-title":"PEGylation of a vesicular stomatitis virus G pseudotyped lentivirus vector prevents inactivation in serum","volume":"78","author":"Croyle","year":"2004","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/sj.gt.3302485","article-title":"Lentiviral vector-mediated gene transfer in adult mouse photoreceptors is impaired by the presence of a physical barrier","volume":"12","author":"Gruter","year":"2005","journal-title":"Gene Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1126\/science.1190897","article-title":"Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa","volume":"329","author":"Busskamp","year":"2010","journal-title":"Science"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1093\/hmg\/10.26.3075","article-title":"Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: The retina as a model","volume":"10","author":"Auricchio","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1002\/jgm.788","article-title":"Retinal cell type expression specificity of HIV-1-derived gene transfer vectors upon subretinal injection in the adult rat: Influence of pseudotyping and promoter","volume":"7","author":"Bemelmans","year":"2005","journal-title":"J. Gene Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/gt.2014.57","article-title":"Retinal transduction profiles by high-capacity viral vectors","volume":"21","author":"Puppo","year":"2014","journal-title":"Gene Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1089\/hum.2009.102","article-title":"Inhibition of choroidal neovascularization via brief subretinal exposure to a newly developed lentiviral vector pseudotyped with Sendai viral envelope proteins","volume":"21","author":"Murakami","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7181","DOI":"10.1128\/JVI.72.9.7181-7190.1998","article-title":"The neural cell adhesion molecule is a receptor for rabies virus","volume":"72","author":"Thoulouze","year":"1998","journal-title":"J. Virol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1099\/0022-1317-77-10-2437","article-title":"Rabies virus binding to the nicotinic acetylcholine receptor alpha subunit demonstrated by virus overlay protein binding assay","volume":"77","author":"Gastka","year":"1996","journal-title":"J. Gen. Virol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1128\/jvi.67.1.530-542.1993","article-title":"Evidence from the anti-idiotypic network that the acetylcholine receptor is a rabies virus receptor","volume":"67","author":"Hanham","year":"1993","journal-title":"J. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/jmr.300030205","article-title":"Rabies virus binding to an acetylcholine receptor alpha-subunit peptide","volume":"3","author":"Lentz","year":"1990","journal-title":"J. Mol. Recognit."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"7250","DOI":"10.1093\/emboj\/17.24.7250","article-title":"Low-affinity nerve-growth factor receptor (P75NTR) can serve as a receptor for rabies virus","volume":"17","author":"Tuffereau","year":"1998","journal-title":"EMBO J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1093\/hmg\/10.19.2109","article-title":"Rabies virus glycoprotein pseudotyping of lentiviral vectors enables retrograde axonal transport and access to the nervous system after peripheral delivery","volume":"10","author":"Mazarakis","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/cne.23761","article-title":"Vesicular stomatitis virus enables gene transfer and transsynaptic tracing in a wide range of organisms","volume":"523","author":"Mundell","year":"2015","journal-title":"J. Comp. Neurol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1089\/10430340360464723","article-title":"Large-scale production of pseudotyped lentiviral vectors using baculovirus GP64","volume":"14","author":"Kumar","year":"2003","journal-title":"Hum. Gene Ther."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/sj.gt.3302170","article-title":"Lentiviral vectors pseudotyped with baculovirus gp64 efficiently transduce mouse cells in vivo and show tropism restriction against hematopoietic cell types in vitro","volume":"11","author":"Schauber","year":"2004","journal-title":"Gene Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.ymthe.2004.12.002","article-title":"Baculovirus GP64-pseudotyped HIV-based lentivirus vectors are stabilized against complement inactivation by codisplay of decay accelerating factor (DAF) or of a GP64-DAF fusion protein","volume":"11","author":"Guibinga","year":"2005","journal-title":"Mol. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Hirano, M., Kato, S., Kobayashi, K., Okada, T., Yaginuma, H., and Kobayashi, K. (2013). Highly efficient retrograde gene transfer into motor neurons by a lentiviral vector pseudotyped with fusion glycoprotein. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075896"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jneumeth.2014.02.015","article-title":"Improved transduction efficiency of a lentiviral vector for neuron-specific retrograde gene transfer by optimizing the junction of fusion envelope glycoprotein","volume":"227","author":"Kato","year":"2014","journal-title":"J. Neurosci. Methods"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1038\/mt.2008.128","article-title":"Targeted cell entry of lentiviral vectors","volume":"16","author":"Funke","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nm1192","article-title":"Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection","volume":"11","author":"Morizono","year":"2005","journal-title":"Nat. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nbt1060","article-title":"Rescue and propagation of fully retargeted oncolytic measles viruses","volume":"23","author":"Nakamura","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/nmeth.1514","article-title":"Specific gene transfer to neurons, endothelial cells and hematopoietic progenitors with lentiviral vectors","volume":"7","author":"Anliker","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/mt.2010.298","article-title":"DARPins: An efficient targeting domain for lentiviral vectors","volume":"19","author":"Munch","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev-pharmtox-010611-134654","article-title":"Designed ankyrin repeat proteins (DARPins): Binding proteins for research, diagnostics, and therapy","volume":"55","author":"Pluckthun","year":"2015","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Kneissl, S., Abel, T., Rasbach, A., Brynza, J., Schneider-Schaulies, J., and Buchholz, C.J. (2012). Measles virus glycoprotein-based lentiviral targeting vectors that avoid neutralizing antibodies. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046667"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"100906","DOI":"10.1016\/j.preteyeres.2020.100906","article-title":"Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities","volume":"82","author":"Mettu","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1097\/ICU.0000000000000763","article-title":"Geographic atrophy: Where we are now and where we are going","volume":"32","author":"Richard","year":"2021","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Pugazhendhi, A., Hubbell, M., Jairam, P., and Ambati, B. (2021). Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031170"},{"key":"ref_132","first-page":"4263795","article-title":"Insights into the Mechanisms Involved in Protective Effects of VEGF-B in Dopaminergic Neurons","volume":"2017","author":"Caballero","year":"2017","journal-title":"Parkinson\u2019s Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"572","DOI":"10.2174\/1389200216666151001120831","article-title":"Pharmacokinetic and Pharmacodynamic Properties of Anti-VEGF Drugs After Intravitreal Injection","volume":"16","author":"Semeraro","year":"2015","journal-title":"Curr. Drug. Metab."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Koponen, S., Kokki, E., Kinnunen, K., and Yla-Herttuala, S. (2021). Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13020219"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1126\/science.285.5425.245","article-title":"Pigment epithelium-derived factor: A potent inhibitor of angiogenesis","volume":"285","author":"Dawson","year":"1999","journal-title":"Science"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1046\/j.1471-4159.1997.68010026.x","article-title":"Pigment epithelium-derived factor protects cultured cerebellar granule cells against glutamate-induced neurotoxicity","volume":"68","author":"Taniwaki","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e781","DOI":"10.1038\/cddis.2013.303","article-title":"Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability","volume":"4","author":"Cachafeiro","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"14064","DOI":"10.1038\/mtm.2014.64","article-title":"Multigenic lentiviral vectors for combined and tissue-specific expression of miRNA- and protein-based antiangiogenic factors","volume":"2","author":"Askou","year":"2015","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1089\/hgtb.2017.079","article-title":"Suppression of Choroidal Neovascularization in Mice by Subretinal Delivery of Multigenic Lentiviral Vectors Encoding Anti-Angiogenic MicroRNAs","volume":"28","author":"Askou","year":"2017","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.omtn.2017.08.016","article-title":"In vivo Knockout of the Vegfa Gene by Lentiviral Delivery of CRISPR\/Cas9 in Mouse Retinal Pigment Epithelium Cells","volume":"9","author":"Holmgaard","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1089\/hum.2008.046","article-title":"Equine infectious anemia viral vector-mediated codelivery of endostatin and angiostatin driven by retinal pigmented epithelium-specific VMD2 promoter inhibits choroidal neovascularization","volume":"20","author":"Kachi","year":"2009","journal-title":"Hum. Gene Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1089\/hum.2016.117","article-title":"Lentiviral Vector Gene Transfer of Endostatin\/Angiostatin for Macular Degeneration (GEM) Study","volume":"28","author":"Campochiaro","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1136\/archdischild-2016-310532","article-title":"Epidemiology of blindness in children","volume":"102","author":"Solebo","year":"2017","journal-title":"Arch. Dis. Child."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1167\/iovs.63.1.37","article-title":"The Long-Noncoding RNA TUG1 Regulates Oxygen-Induced Retinal Neovascularization in Mice via MiR-299","volume":"63","author":"Wang","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s10456-018-9626-5","article-title":"Correction to: Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy","volume":"21","author":"Simmons","year":"2018","journal-title":"Angiogenesis"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.ajpath.2013.05.011","article-title":"Short hairpin RNA-mediated knockdown of VEGFA in Muller cells reduces intravitreal neovascularization in a rat model of retinopathy of prematurity","volume":"183","author":"Wang","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1038\/s41598-018-20278-4","article-title":"Targeted Knockdown of Overexpressed VEGFA or VEGF164 in Muller cells maintains retinal function by triggering different signaling mechanisms","volume":"8","author":"Becker","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1084\/jem.20022027","article-title":"VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization","volume":"198","author":"Ishida","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1167\/iovs.13-13755","article-title":"Targeting Muller cell-derived VEGF164 to reduce intravitreal neovascularization in the rat model of retinopathy of prematurity","volume":"55","author":"Jiang","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.neuroscience.2022.03.010","article-title":"Gene Therapy for Neurological Disease: State of the Art and Opportunities for Next-generation Approaches","volume":"490","author":"Morris","year":"2022","journal-title":"Neuroscience"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.preteyeres.2010.03.004","article-title":"The molecular basis of human retinal and vitreoretinal diseases","volume":"29","author":"Berger","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"7812","DOI":"10.1128\/JVI.73.9.7812-7816.1999","article-title":"Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer","volume":"73","author":"Takahashi","year":"1999","journal-title":"J. Virol."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Bemelmans, A.P., Kostic, C., Crippa, S.V., Hauswirth, W.W., Lem, J., Munier, F.L., Seeliger, M.W., Wenzel, A., and Arsenijevic, Y. (2006). Lentiviral gene transfer of RPE65 rescues survival and function of cones in a mouse model of Leber congenital amaurosis. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030347"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Kostic, C., Crippa, S.V., Pignat, V., Bemelmans, A.P., Samardzija, M., Grimm, C., Wenzel, A., and Arsenijevic, Y. (2011). Gene therapy regenerates protein expression in cone photoreceptors in Rpe65(R91W\/R91W) mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016588"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"8890","DOI":"10.1038\/s41598-020-65657-y","article-title":"Lentiviral mediated RPE65 gene transfer in healthy hiPSCs-derived retinal pigment epithelial cells markedly increased RPE65 mRNA, but modestly protein level","volume":"10","author":"Udry","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nature24644","article-title":"Programmable base editing of A*T to G * C in genomic DNA without DNA cleavage","volume":"551","author":"Gaudelli","year":"2017","journal-title":"Nature"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41551-020-00632-6","article-title":"Restoration of visual function in adult mice with an inherited retinal disease via adenine base editing","volume":"5","author":"Suh","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"eaax1210","DOI":"10.1126\/sciadv.aax1210","article-title":"CRISPR-Cas9-mediated therapeutic editing of Rpe65 ameliorates the disease phenotypes in a mouse model of Leber congenital amaurosis","volume":"5","author":"Jo","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/374060a0","article-title":"Defective myosin VIIA gene responsible for Usher syndrome type 1B","volume":"374","author":"Weil","year":"1995","journal-title":"Nature"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/sj.gt.3302897","article-title":"Lentiviral gene replacement therapy of retinas in a mouse model for Usher syndrome type 1B","volume":"14","author":"Hashimoto","year":"2007","journal-title":"Gene Ther."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/gt.2008.78","article-title":"Correction of the disease phenotype in the mouse model of Stargardt disease by lentiviral gene therapy","volume":"15","author":"Kong","year":"2008","journal-title":"Gene Ther."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ajo.2022.02.013","article-title":"Three-year safety results of SAR422459 (EIAV-ABCA4) gene therapy in patients with ABCA4-associated Stargardt disease: An open-label dose-escalation phase I\/IIa clinical trial, cohorts 1-5","volume":"240","author":"Parker","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/tvst.5.5.10","article-title":"Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial","volume":"5","author":"Parker","year":"2016","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.cell.2015.03.023","article-title":"Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis","volume":"161","author":"Fridlich","year":"2015","journal-title":"Cell"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/ng1386","article-title":"Identification and characterization of rod-derived cone viability factor","volume":"36","author":"Leveillard","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nn.2234","article-title":"Stimulation of the insulin\/mTOR pathway delays cone death in a mouse model of retinitis pigmentosa","volume":"12","author":"Punzo","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"E517","DOI":"10.1073\/pnas.1218933110","article-title":"Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement","volume":"110","author":"Cideciyan","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/81555","article-title":"Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa","volume":"26","author":"Gal","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1006\/nbdi.2000.0328","article-title":"Homozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis","volume":"7","author":"Nandrot","year":"2000","journal-title":"Neurobiol. Dis."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1073\/pnas.88.3.723","article-title":"Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse","volume":"88","author":"Connell","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0896-6273(91)90122-G","article-title":"The retinal degeneration slow (rds) gene product is a photoreceptor disc membrane-associated glycoprotein","volume":"6","author":"Travis","year":"1991","journal-title":"Neuron"},{"key":"ref_172","first-page":"1112","article-title":"The effect of C3 transgene expression on actin and cellular adhesions in cultured human trabecular meshwork cells and on outflow facility in organ cultured monkey eyes","volume":"11","author":"Liu","year":"2005","journal-title":"Mol. Vis."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1167\/iovs.14-15909","article-title":"Viral Vector Effects on Exoenzyme C3 Transferase-Mediated Actin Disruption and on Outflow Facility","volume":"56","author":"Slauson","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0002-9394(89)90805-2","article-title":"Trabecular repopulation by anterior trabecular meshwork cells after laser trabeculoplasty","volume":"107","author":"Acott","year":"1989","journal-title":"Am. J. Ophthalmol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40662-019-0156-z","article-title":"Identification, quantification and age-related changes of human trabecular meshwork stem cells","volume":"6","author":"Sundaresan","year":"2019","journal-title":"Eye Vis."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/mt.2009.278","article-title":"Prostaglandin pathway gene therapy for sustained reduction of intraocular pressure","volume":"18","author":"Barraza","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1167\/tvst.10.8.14","article-title":"Long-Term Decrease of Intraocular Pressure in Rats by Viral Delivery of miR-146a","volume":"10","author":"Luna","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1167\/iovs.09-4874","article-title":"Modulation of inflammatory markers by miR-146a during replicative senescence in trabecular meshwork cells","volume":"51","author":"Li","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1002\/jcp.22476","article-title":"MicroRNA-24 regulates the processing of latent TGFbeta1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN","volume":"226","author":"Luna","year":"2011","journal-title":"J. Cell Physiol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"859","DOI":"10.3109\/02713683.2014.884593","article-title":"Prospects for lentiviral vector mediated prostaglandin F synthase gene delivery in monkey eyes in vivo","volume":"39","author":"Lee","year":"2014","journal-title":"Curr. Eye Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s00417-003-0835-1","article-title":"The influence of Latanoprost 0.005% on aqueous humor flow and outflow facility in glaucoma patients: A double-masked placebo-controlled clinical study","volume":"242","author":"Dinslage","year":"2004","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1167\/iovs.17-22074","article-title":"Proteasome Inhibition Increases the Efficiency of Lentiviral Vector-Mediated Transduction of Trabecular Meshwork","volume":"59","author":"Aktas","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_183","first-page":"760","article-title":"CNTF, not other trophic factors, promotes axonal regeneration of axotomized retinal ganglion cells in adult hamsters","volume":"40","author":"Cui","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/S0042-6989(97)00364-7","article-title":"Effects of GDNF on retinal ganglion cell survival following axotomy","volume":"38","author":"Koeberle","year":"1998","journal-title":"Vis. Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/0006-8993(93)90695-J","article-title":"Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo","volume":"602","author":"Mey","year":"1993","journal-title":"Brain Res."},{"key":"ref_186","first-page":"489","article-title":"Effects of axotomy and intraocular administration of NT-4, NT-3, and brain-derived neurotrophic factor on the survival of adult rat retinal ganglion cells. A quantitative in vivo study","volume":"37","author":"Salvador","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/10430340050016256","article-title":"Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson\u2019s disease","volume":"11","author":"Deglon","year":"2000","journal-title":"Hum. Gene Ther."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1006\/nbdi.2001.0388","article-title":"Neuroprotective effect of a CNTF-expressing lentiviral vector in the quinolinic acid rat model of Huntington\u2019s disease","volume":"8","author":"Zala","year":"2001","journal-title":"Neurobiol. Dis."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1089\/hum.2010.132","article-title":"Pigment epithelium-derived factor gene therapy targeting retinal ganglion cell injuries: Neuroprotection against loss of function in two animal models","volume":"22","author":"Miyazaki","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"104","DOI":"10.2174\/1566523221666210423084233","article-title":"Gene Therapy in the Anterior Eye Segment","volume":"22","author":"Amador","year":"2022","journal-title":"Curr. Gene Ther."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/ncb3290","article-title":"Chronic inflammation imposes aberrant cell fate in regenerating epithelia through mechanotransduction","volume":"18","author":"Nowell","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.exer.2011.09.009","article-title":"Cell signaling in regulation of the barrier integrity of the corneal endothelium","volume":"95","author":"Srinivas","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/nature05249","article-title":"Corneal avascularity is due to soluble VEGF receptor-1","volume":"443","author":"Ambati","year":"2006","journal-title":"Nature"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1111\/j.1600-6143.2007.01897.x","article-title":"Corneal graft rejection is accompanied by apoptosis of the endothelium and is prevented by gene therapy with bcl-xL","volume":"7","author":"Barcia","year":"2007","journal-title":"Am. J. Transplant."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1089\/hum.2010.079","article-title":"Corneal endothelial cells are protected from apoptosis by gene therapy","volume":"22","author":"Fuchsluger","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"100987","DOI":"10.1016\/j.preteyeres.2021.100987","article-title":"Approaches for corneal endothelium regenerative medicine","volume":"87","author":"Catala","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.4049\/jimmunol.175.4.2219","article-title":"Prolongation of sheep corneal allograft survival by transfer of the gene encoding ovine IL-12-p40 but not IL-4 to donor corneal endothelium","volume":"175","author":"Klebe","year":"2005","journal-title":"J. Immunol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1442-9071.2010.02261.x","article-title":"Lentivirus-mediated gene transfer of interleukin 10 to the ovine and human cornea","volume":"38","author":"Parker","year":"2010","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"406","DOI":"10.3109\/09273948.2012.723109","article-title":"Roles of IL-10 in ocular inflammations: A review","volume":"20","author":"Ghasemi","year":"2012","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1097\/00007890-200105150-00006","article-title":"Prolongation of sheep corneal allograft survival by ex vivo transfer of the gene encoding interleukin-10","volume":"71","author":"Klebe","year":"2001","journal-title":"Transplantation"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1111\/j.1600-6143.2011.03948.x","article-title":"Role of lentivirus-mediated overexpression of programmed death-ligand 1 on corneal allograft survival","volume":"12","author":"Nosov","year":"2012","journal-title":"Am. J. Transplant."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1089\/hum.2019.220","article-title":"Can Adeno-Associated Viral Vectors Deliver Effectively Large Genes?","volume":"31","author":"Tornabene","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"857276","DOI":"10.3389\/fimmu.2022.857276","article-title":"Overcoming the Challenges Imposed by Humoral Immunity to AAV Vectors to Achieve Safe and Efficient Gene Transfer in Seropositive Patients","volume":"13","author":"Gross","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.omtm.2022.02.011","article-title":"Testing preexisting antibodies prior to AAV gene transfer therapy: Rationale, lessons and future considerations","volume":"25","author":"Mendell","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/8\/1605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:36Z","timestamp":1760140836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/8\/1605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,31]]},"references-count":204,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["pharmaceutics14081605"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14081605","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,31]]}}}