{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:49:33Z","timestamp":1775738973357,"version":"3.50.1"},"reference-count":147,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010310","name":"E. Matilda Ziegler Foundation for the Blind","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010627","name":"Barr Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010627","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006325","name":"ARVO Foundation for Eye Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007817","name":"Alcon Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007817","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011718","name":"Macular Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genome Ed."],"abstract":"<jats:p>Among genome engineering tools, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based approaches have been widely adopted for translational studies due to their robustness, precision, and ease of use. When delivered to diseased tissues with a viral vector such as adeno-associated virus, direct genome editing can be efficiently achieved <jats:italic>in vivo<\/jats:italic> to treat different ophthalmic conditions. While CRISPR has been actively explored as a strategy for treating inherited retinal diseases, with the first human trial recently initiated, its applications for complex, multifactorial conditions such as ocular angiogenesis has been relatively limited. Currently, neovascular retinal diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular age-related macular degeneration, which together constitute the majority of blindness in developed countries, are managed with frequent and costly injections of anti-vascular endothelial growth factor (anti-VEGF) agents that are short-lived and burdensome for patients. By contrast, CRISPR technology has the potential to suppress angiogenesis <jats:italic>permanently<\/jats:italic>, with the added benefit of targeting intracellular signals or regulatory elements, cell-specific delivery, and multiplexing to disrupt different pro-angiogenic factors simultaneously. However, the prospect of permanently suppressing physiologic pathways, the unpredictability of gene editing efficacy, and concerns for off-target effects have limited enthusiasm for these approaches. Here, we review the evolution of gene therapy and advances in adapting CRISPR platforms to suppress retinal angiogenesis. We discuss different Cas9 orthologs, delivery strategies, and different genomic targets including VEGF, VEGF receptor, and HIF-1\u03b1, as well as the advantages and disadvantages of genome editing vs. conventional gene therapies for multifactorial disease processes as compared to inherited monogenic retinal disorders. Lastly, we describe barriers that must be overcome to enable effective adoption of CRISPR-based strategies for the management of ocular angiogenesis.<\/jats:p>","DOI":"10.3389\/fgeed.2020.594984","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T08:55:23Z","timestamp":1608627323000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["CRISPR Technology for Ocular Angiogenesis"],"prefix":"10.3389","volume":"2","author":[{"given":"Sook Hyun","family":"Chung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Ni","family":"Sin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor","family":"Ngo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn","family":"Yiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/nature24049","article-title":"RNA targeting with CRISPR\u2013Cas13","volume":"550","author":"Abudayyeh","year":"2017","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1126\/science.aax7063","article-title":"A cytosine deaminase for programmable single-base RNA editing","volume":"365","author":"Abudayyeh","year":"2019","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"eaaw5328","DOI":"10.1126\/scitranslmed.aaw5328","article-title":"Immunity to CRISPR-Cas9","volume":"11","author":"Attenello","year":"2019","journal-title":"Sci. Transl. Med"},{"key":"B4","doi-asserted-by":"publisher","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":"B5","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1056\/NEJMoa1414221","article-title":"Long-term effect of gene therapy on leber's congenital amaurosis","volume":"372","author":"Bainbridge","year":"2015","journal-title":"N. Engl. J. Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1056\/NEJMoa0802268","article-title":"Effect of gene therapy on visual function in leber's congenital amaurosis","volume":"358","author":"Bainbridge","year":"2008","journal-title":"N. Engl. J. Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/j.ophtha.2020.04.017","article-title":"Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab","volume":"127","author":"Baumal","year":"2020","journal-title":"Ophthalmology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"120r","DOI":"10.1126\/scitranslmed.3002865","article-title":"AAV2 gene therapy readministration in three adults with congenital blindness","volume":"4","author":"Bennett","year":"2012","journal-title":"Sci. Transl. Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ghir.2018.02.002","article-title":"Somatolactogens and diabetic retinopathy","volume":"41","author":"Bermea","year":"2018","journal-title":"Growth Horm. IGF Res"},{"key":"B10","article-title":"Phase 1 study of intravitreal gene therapy with ADVM-022 for neovascular AMD (OPTIC trial)","volume-title":"Presented at the Angiogenesis, Exudation, and Degeneration 2020","author":"Boyer","year":"2020"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.ophtha.2010.02.022","article-title":"Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study","volume":"117","author":"Brown","year":"2010","journal-title":"Ophthalmology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.ophtha.2008.10.018","article-title":"Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study","volume":"116","author":"Brown","year":"2009","journal-title":"Ophthalmology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1016\/j.ophtha.2013.02.034","article-title":"Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE","volume":"120","author":"Brown","year":"2013","journal-title":"Ophthalmology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.oret.2017.04.004","article-title":"Bevacizumab injection in patients with neovascular age-related macular degeneration increases angiogenic biomarkers","volume":"2","author":"Cabral","year":"2018","journal-title":"Ophthalmol. Retina"},{"key":"B15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40942-017-0084-9","article-title":"Retinal and choroidal angiogenesis: a review of new targets","volume":"3","author":"Cabral","year":"2017","journal-title":"Int. J. Retina Vitr"},{"key":"B16","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1089\/jop.2018.0062","article-title":"Double-masked, randomized, phase 2 evaluation of abicipar pegol (an anti-VEGF DARPin therapeutic) in neovascular age-related macular degeneration","volume":"34","author":"Callanan","year":"2018","journal-title":"J. Ocul. Pharmacol. Ther"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/j.ophtha.2010.02.021","article-title":"Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study","volume":"117","author":"Campochiaro","year":"2010","journal-title":"Ophthalmology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/j.ophtha.2019.03.036","article-title":"The port delivery system with ranibizumab for neovascular age-related macular degeneration","volume":"126","author":"Campochiaro","year":"2019","journal-title":"Ophthalmology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1001\/archopht.1990.01070130025012","article-title":"Micrococcus endophthalmitis","volume":"108","author":"Cartwright","year":"1990","journal-title":"Arch. Ophthalmol. Chic."},{"key":"B20","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1021\/acs.molpharmaceut.9b,01191","article-title":"Ocular half-life of intravitreal biologics in humans and other species: meta-analysis and model-based prediction","volume":"17","author":"Caruso","year":"2020","journal-title":"Mol. Pharm."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1056\/NEJMoa1102673","article-title":"Ranibizumab and bevacizumab for neovascular age-related macular degeneration","volume":"364","author":"Martin","year":"2011","journal-title":"N. Engl. J. Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1038\/nm1075","article-title":"Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1","volume":"10","author":"Ceradini","year":"2004","journal-title":"Nat. Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41591-018-0326-x","article-title":"Identification of preexisting adaptive immunity to Cas9 proteins in humans","volume":"25","author":"Charlesworth","year":"2019","journal-title":"Nat. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1073\/pnas.1912220117","article-title":"Near-infrared optogenetic engineering of photothermal nanoCRISPR for programmable genome editing","volume":"117","author":"Chen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"B25","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1038\/nmeth.3993","article-title":"A multifunctional AAV\u2013CRISPR\u2013Cas9 and its host response","volume":"13","author":"Chew","year":"2016","journal-title":"Nat. Methods"},{"key":"B26","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1101\/gr.162339.113","article-title":"Analysis of off-target effects of CRISPR\/Cas-derived RNA-guided endonucleases and nickases","volume":"24","author":"Cho","year":"2014","journal-title":"Genome Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1101\/gr.246900.118","article-title":"Targeted delivery of CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance","volume":"29","author":"Chung","year":"2019","journal-title":"Genome Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.omtm.2020.01.006","article-title":"Factors impacting efficacy of AAV-mediated CRISPR-based genome editing for treatment of choroidal neovascularization","volume":"17","author":"Chung","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev"},{"key":"B29","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.ophtha.2015.09.035","article-title":"Intravitreal aflibercept for macular edema following branch retinal vein occlusion: 52-week results of the VIBRANT study","volume":"123","author":"Clark","year":"2016","journal-title":"Ophthalmology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/bjophthalmol-2020-316511","article-title":"APEX: a phase II randomised clinical trial evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular degeneration","author":"Cohen","year":"2020","journal-title":"Br. J. Ophthalmol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.ebiom.2016.11.016","article-title":"Phase 2a randomized clinical trial: safety and post hoc analysis of subretinal rAAV.sFLT-1 for wet age-related macular degeneration","volume":"14","author":"Constable","year":"2016","journal-title":"EBioMedicine"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1126\/science.aaq0180","article-title":"RNA editing with CRISPR-Cas13","volume":"358","author":"Cox","year":"2017","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3497","DOI":"10.1038\/s41467-018-05843-9","article-title":"Cas9 immunity creates challenges for CRISPR gene editing therapies","volume":"9","author":"Crudele","year":"2018","journal-title":"Nat. Commun"},{"key":"B35","doi-asserted-by":"publisher","first-page":"189r","DOI":"10.1126\/scitranslmed.3005708","article-title":"In vivo-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":"B36","doi-asserted-by":"publisher","first-page":"4901","DOI":"10.1172\/JCI129085","article-title":"AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression","volume":"130","author":"Ding","year":"2019","journal-title":"J. Clin. Invest"},{"key":"B37","doi-asserted-by":"publisher","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":"B38","doi-asserted-by":"publisher","first-page":"892043","DOI":"10.1155\/2015\/892043","article-title":"Ocular angiogenesis","volume":"2015","author":"Dreyfuss","year":"2015","journal-title":"J. Ophthalmol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2020.06.028","article-title":"HAWK and HARRIER: 96-Week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration","author":"Dugel","year":"2020","journal-title":"Ophthalmology."},{"key":"B40","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s11892-019-1276-5","article-title":"Emerging concepts in the treatment of diabetic retinopathy","volume":"19","author":"Ellis","year":"2019","journal-title":"Curr. Diab. Rep"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.1084\/jem.20150718","article-title":"Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin","volume":"212","author":"Frye","year":"2015","journal-title":"J. Exp. Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/nbt.2808","article-title":"Improving CRISPR-Cas nuclease specificity using truncated guide RNAs","volume":"32","author":"Fu","year":"2014","journal-title":"Nat. Biotechnol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.ophtha.2014.09.034","article-title":"One-year outcomes with half-dose verteporfin photodynamic therapy for chronic central serous chorioretinopathy","volume":"122","author":"Fujita","year":"2015","journal-title":"Ophthalmology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1016\/0042-6989(93)90144-l","article-title":"Assessment of foveal cone photoreceptors in stargardt's macular dystrophy using a small dot detection task","volume":"33","author":"Geller","year":"1993","journal-title":"Vision Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.cell.2013.06.044","article-title":"CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes","volume":"154","author":"Gilbert","year":"2013","journal-title":"Cell"},{"key":"B46","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/path.1778","article-title":"Up-regulation of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor 1 (HIF-1)","volume":"206","author":"Greijer","year":"2005","journal-title":"J. Pathol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.ymthe.2018.11.003","article-title":"Preclinical evaluation of ADVM-022, a novel gene therapy approach to treating wet age-related macular degeneration","volume":"27","author":"Grishanin","year":"2019","journal-title":"Mol. Ther"},{"key":"B48","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.ophtha.2014.11.007","article-title":"Growth of geographic atrophy in the comparison of age-related macular degeneration treatments trials","volume":"122","author":"Grunwald","year":"2015","journal-title":"Ophthalmology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.ophtha.2005.10.052","article-title":"Ranibizumab for treatment of neovascular age-related macular degeneration","volume":"113","author":"Heier","year":"2006","journal-title":"Ophthalmology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1016\/j.ophtha.2014.01.027","article-title":"Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study","volume":"121","author":"Heier","year":"2014","journal-title":"Ophthalmology"},{"key":"B51","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ophtha.2019.09.021","article-title":"Intravitreal combined aflibercept + anti\u2013platelet-derived growth factor receptor \u03b2 for neovascular age-related macular degeneration","volume":"127","author":"Heier","year":"2020","journal-title":"Ophthalmology"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1016\/S0140-6736(13)60178-6","article-title":"Retinopathy of prematurity","volume":"382","author":"Hellstr\u00f6m","year":"2013","journal-title":"Lancet"},{"key":"B53","doi-asserted-by":"publisher","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":"B54","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1248\/bpb.b18-00913","article-title":"Adeno associated virus (AAV) as a tool for clinical and experimental delivery of target genes into the mammalian retina","volume":"42","author":"Hori","year":"2019","journal-title":"Biol. Pharm. Bull"},{"key":"B55","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41467-017-00140-3","article-title":"Genome editing abrogates angiogenesis in vivo","volume":"8","author":"Huang","year":"","journal-title":"Nat. Commun"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1167\/iovs.16-20537","article-title":"Editing VEGFR2 blocks VEGF-induced activation of akt and tube formation","volume":"58","author":"Huang","year":"","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B57","doi-asserted-by":"publisher","first-page":"5430","DOI":"10.1167\/iovs.03-0609","article-title":"RPE cells modulate subretinal neovascularization, but do not cause regression in mice with sustained expression of VEGF","volume":"44","author":"Ida","year":"2003","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B58","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1167\/iovs.13-13755","article-title":"Targeting M\u00fcller cell-derived VEGF164 to reduce intravitreal neovascularization in the rat model of retinopathy of prematurity","volume":"55","author":"Jiang","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B59","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.ymthe.2018.10.009","article-title":"Long-term effects of in vivo genome editing in the mouse retina using campylobacter jejuni cas9 expressed via adeno-associated virus","volume":"27","author":"Jo","year":"2019","journal-title":"Mol. Ther"},{"key":"B60","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.bbcan.2015.09.003","article-title":"CRISPR\/Cas9 system as an innovative genetic engineering tool: enhancements in sequence specificity and delivery methods","volume":"1856","author":"Jo","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"B61","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.ajo.2007.08.012","article-title":"Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results","volume":"144","author":"Kaiser","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"41","DOI":"10.4155\/tde.14.91","article-title":"PLGA: a unique polymer for drug delivery","volume":"6","author":"Kapoor","year":"2015","journal-title":"Ther. Deliv"},{"key":"B63","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1001\/jamaophthalmol.2020.2699","article-title":"Efficacy of every four monthly and quarterly dosing of faricimab vs ranibizumab in neovascular age-related macular degeneration: the STAIRWAY phase 2 randomized clinical trial","volume":"138","author":"Khanani","year":"2020","journal-title":"JAMA Ophthalmol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"14500","DOI":"10.1038\/ncomms14500","article-title":"In vivo genome editing with a small Cas9 orthologue derived from campylobacter jejuni","volume":"8","author":"Kim","year":"2017","journal-title":"Nat. Commun"},{"key":"B65","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1101\/gr.219089.116","article-title":"Genome surgery using Cas9 ribonucleoproteins for the treatment of age-related macular degeneration","volume":"27","author":"Kim","year":"","journal-title":"Genome Res"},{"key":"B66","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/nbt.3816","article-title":"Highly efficient RNA-guided base editing in mouse embryos","volume":"35","author":"Kim","year":"","journal-title":"Nat. Biotechnol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1101\/gr.171322.113","article-title":"Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins","volume":"24","author":"Kim","year":"2014","journal-title":"Genome Res"},{"key":"B68","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/nature16526","article-title":"High-fidelity CRISPR-Cas9 variants with undetectable genome-wide off-targets","volume":"529","author":"Kleinstiver","year":"2016","journal-title":"Nature"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1097\/IAE.0b013e31824f91e8","article-title":"EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy","volume":"32","author":"Koh","year":"2012","journal-title":"Retina"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1038\/s41467-018-04175-y","article-title":"CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration","volume":"9","author":"Koo","year":"2018","journal-title":"Nat. Commun"},{"key":"B71","doi-asserted-by":"publisher","first-page":"609","DOI":"10.15252\/emmm.201506078","article-title":"A brain microvasculature endothelial cell-specific viral vector with the potential to treat neurovascular and neurological diseases","volume":"8","author":"K\u00f6rbelin","year":"2016","journal-title":"EMBO Mol. Med"},{"key":"B72","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1016\/j.ophtha.2014.05.006","article-title":"Intravitreal aflibercept for diabetic macular edema","volume":"121","author":"Korobelnik","year":"","journal-title":"Ophthalmology"},{"key":"B73","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.ophtha.2013.08.012","article-title":"Intravitreal aflibercept injection for macular edema resulting from central retinal vein occlusion: one-year results of the phase 3 GALILEO study","volume":"121","author":"Korobelnik","year":"","journal-title":"Ophthalmology"},{"key":"B74","doi-asserted-by":"publisher","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":"B75","doi-asserted-by":"publisher","first-page":"4213","DOI":"10.1172\/JCI65157","article-title":"Targeted deletion of Vegfa in adult mice induces vision loss","volume":"122","author":"Kurihara","year":"2012","journal-title":"J. Clin. Invest"},{"key":"B76","doi-asserted-by":"publisher","first-page":"e0207902","DOI":"10.1371\/journal.pone.0207902","article-title":"Correction: aqueous humor cytokine levels in patients with diabetic macular edema refractory to anti-VEGF treatment","volume":"13","author":"Kwon","year":"2018","journal-title":"PLoS ONE"},{"key":"B77","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1038\/gt.2011.169","article-title":"Preclinical safety evaluation of subretinal AAV2.sFlt-1 in non-human primates","volume":"19","author":"Lai","year":"2012","journal-title":"Gene Ther"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1261\/rna.071704.119","article-title":"Tissue-restricted genome editing in vivo specified by microRNA-repressible anti-CRISPR proteins","volume":"25","author":"Lee","year":"2019","journal-title":"RNA"},{"key":"B79","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ajo.2019.11.031","article-title":"Retinal vessel density in exudative and nonexudative age-related macular degeneration on optical coherence tomography angiography","volume":"212","author":"Lee","year":"2020","journal-title":"Am. J. Ophthalmol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.omtm.2018.11.009","article-title":"A self-deleting AAV-CRISPR system for in vivo genome editing","volume":"12","author":"Li","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1016\/j.ymthe.2020.04.017","article-title":"AAV-CRISPR gene editing is negated by pre-existing immunity to Cas9","volume":"28","author":"Li","year":"2020","journal-title":"Mol. Ther"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1089\/hum.2019.021","article-title":"Utility of self-destructing CRISPR\/cas constructs for targeted gene editing in the retina","volume":"30","author":"Li","year":"2019","journal-title":"Hum. Gene Ther"},{"key":"B83","doi-asserted-by":"publisher","first-page":"570917","DOI":"10.3389\/fncel.2020.570917","article-title":"Comparison of CRISPR\/cas endonucleases for in vivo retinal gene editing","volume":"14","author":"Li","year":"2020","journal-title":"Front. Cell. Neurosci"},{"key":"B84","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.ymthe.2017.12.002","article-title":"AAV8-antiVEGFfab ocular gene transfer for neovascular age-related macular degeneration","volume":"26","author":"Liu","year":"2018","journal-title":"Mol. Ther"},{"key":"B85","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/mt.2010.258","article-title":"Preclinical safety evaluation of AAV2-sFLT01\u2014 a gene therapy for age-related macular degeneration","volume":"19","author":"MacLachlan","year":"2011","journal-title":"Mol. Ther"},{"key":"B86","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41591-018-0327-9","article-title":"Development of a gene-editing approach to restore vision loss in leber congenital amaurosis type 10","volume":"25","author":"Maeder","year":"2019","journal-title":"Nat. Med"},{"key":"B87","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1056\/NEJMoa0802315","article-title":"Safety and efficacy of gene transfer for leber's congenital amaurosis","volume":"358","author":"Maguire","year":"2008","journal-title":"N. Engl. J. Med"},{"key":"B88","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/nbt.2675","article-title":"CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering","volume":"31","author":"Mali","year":"","journal-title":"Nat. Biotechnol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1126\/science.1232033","article-title":"RNA-Guided human genome engineering via Cas9","volume":"339","author":"Mali","year":"","journal-title":"Science"},{"key":"B90","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1182\/blood-2004-07-2958","article-title":"Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1","volume":"105","author":"Manalo","year":"2005","journal-title":"Blood"},{"key":"B91","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.stem.2016.01.022","article-title":"CRISPR interference efficiently induces specific and reversible gene silencing in human iPSCs","volume":"18","author":"Mandegar","year":"2016","journal-title":"Cell Stem Cell"},{"key":"B92","first-page":"13","article-title":"Vascular endothelial growth factor and ocular neovascularization. Am. J","volume":"151","author":"Miller","year":"1997","journal-title":"Pathol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.colsurfb.2017.07.038","article-title":"Recent applications of PLGA based nanostructures in drug delivery","volume":"159","author":"Mir","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"B94","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s00417-013-2495-0","article-title":"Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes","volume":"252","author":"Moisseiev","year":"2014","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.preteyeres.2009.12.002","article-title":"The multifunctional choroid","volume":"29","author":"Nickla","year":"2010","journal-title":"Prog. Retin. Eye Res"},{"key":"B96","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1006\/mthe.2001.0424","article-title":"Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells","volume":"4","author":"Nicklin","year":"2001","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther"},{"key":"B97","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/nbt.2673","article-title":"High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity","volume":"31","author":"Pattanayak","year":"2013","journal-title":"Nat. Biotechnol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1159\/000479157","article-title":"Subretinal injection: a review on the novel route of therapeutic delivery for vitreoretinal diseases","volume":"58","author":"Peng","year":"2017","journal-title":"Ophthalmic Res"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1016\/S0140-6736(15)00345-1","article-title":"Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial","volume":"386","author":"Rakoczy","year":"2015","journal-title":"Lancet Lond. Engl"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.cell.2013.08.021","article-title":"Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity","volume":"154","author":"Ran","year":"2013","journal-title":"Cell"},{"key":"B101","doi-asserted-by":"publisher","first-page":"5836","DOI":"10.1167\/iovs.13-12557","article-title":"Relationship between foveal cone structure and clinical measures of visual function in patients with inherited retinal degenerations","volume":"54","author":"Ratnam","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B102","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3109\/08977199709021522","article-title":"Detection of vascular endothelial growth factor (VEGF) protein in vascular and non-vascular cells of the normal and oxygen-injured rat retina","volume":"14","author":"Robbins","year":"1997","journal-title":"Growth Factors Chur Switz"},{"key":"B103","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.3892\/ijmm.2019.4112","article-title":"Genome editing: a perspective on the application of CRISPR\/Cas9 to study human diseases (review)","volume":"43","author":"Rodr\u00edguez-Rodr\u00edguez","year":"2019","journal-title":"Int. J. Mol. Med"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"Ranibizumab for neovascular age-related macular degeneration","volume":"355","author":"Rosenfeld","year":"2006","journal-title":"N. Engl. J. Med"},{"key":"B105","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/j.ophtha.2019.03.023","article-title":"Simultaneous inhibition of angiopoietin-2 and vascular endothelial growth factor-A with faricimab in diabetic macular edema","volume":"126","author":"Sahni","year":"2019","journal-title":"Ophthalmology"},{"key":"B106","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1146\/annurev.med.54.101601.152418","article-title":"Angiogenesis in ischemic and neoplastic disorders","volume":"54","author":"Semenza","year":"2003","journal-title":"Annu. Rev. Med"},{"key":"B107","doi-asserted-by":"publisher","first-page":"4564","DOI":"10.1172\/JCI74527","article-title":"Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature","volume":"124","author":"Shen","year":"2014","journal-title":"J. Clin. Invest"},{"key":"B108","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1177\/1947601911423031","article-title":"Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis","volume":"2","author":"Shibuya","year":"2011","journal-title":"Genes Cancer"},{"key":"B109","doi-asserted-by":"publisher","first-page":"e1701620","DOI":"10.1126\/sciadv.1701620","article-title":"Disabling Cas9 by an anti-CRISPR DNA mimic","volume":"3","author":"Shin","year":"2017","journal-title":"Sci. Adv"},{"key":"B110","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1016\/j.ebiom.2015.09.042","article-title":"Cyclic AMP response element binding protein mediates pathological retinal neovascularization via modulating DLL4-NOTCH1 signaling","volume":"2","author":"Singh","year":"2015","journal-title":"EBioMedicine"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1001\/jamaophthalmol.2018.2650","article-title":"Association between the cilioretinal artery and choroidal neovascularization in age-related macular degeneration: a secondary analysis from the age-related eye disease study","volume":"136","author":"Snyder","year":"2018","journal-title":"JAMA Ophthalmol"},{"key":"B112","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1016\/S0140-6736(19)31344-3","article-title":"Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial","volume":"394","author":"Stahl","year":"2019","journal-title":"Lancet Lond. Engl"},{"key":"B113","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/mt.2008.283","article-title":"Detection of intact rAAV particles up to 6 years after successful gene transfer in the retina of dogs and primates","volume":"17","author":"Stieger","year":"2009","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther"},{"key":"B114","first-page":"290","article-title":"Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity","volume":"37","author":"Stone","year":"1996","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B115","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1089\/hum.2011.060","article-title":"Surgical approaches to gene and stem cell therapy for retinal disease","volume":"22","author":"Stout","year":"2011","journal-title":"Hum. Gene Ther"},{"key":"B116","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1136\/bjophthalmol-2013-304670","article-title":"Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration","volume":"98","author":"Suzuki","year":"2014","journal-title":"Br. J. Ophthalmol"},{"key":"B117","doi-asserted-by":"publisher","first-page":"20969","DOI":"10.1073\/pnas.1906843116","article-title":"Rationally engineered Staphylococcus aureus Cas9 nucleases with high genome-wide specificity","volume":"116","author":"Tan","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"B118","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1038\/s41467-018-04048-4","article-title":"RNA-guided transcriptional silencing in vivo with S. aureus CRISPR-Cas9 repressors","volume":"9","author":"Thakore","year":"2018","journal-title":"Nat. Commun"},{"key":"B119","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1586\/17512433.2014.890047","article-title":"Current and investigational pharmacotherapeutic approaches for modulating retinal angiogenesis","volume":"7","author":"Todorich","year":"2014","journal-title":"Expert Rev. Clin. Pharmacol"},{"key":"B120","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1002\/emmm.201302948","article-title":"Effective delivery of large genes to the retina by dual AAV vectors","volume":"6","author":"Trapani","year":"2014","journal-title":"EMBO Mol. Med"},{"key":"B121","first-page":"1329","article-title":"Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials\u2013TAP report. Arch","volume":"117","year":"1999","journal-title":"Ophthalmol"},{"key":"B122","doi-asserted-by":"publisher","first-page":"e74","DOI":"10.1093\/nar\/gkz267","article-title":"CRISPRai for simultaneous gene activation and inhibition to promote stem cell chondrogenesis and calvarial bone regeneration","volume":"47","author":"Truong","year":"2019","journal-title":"Nucl. Acids Res"},{"key":"B123","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nbt.3117","article-title":"GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases","volume":"33","author":"Tsai","year":"2015","journal-title":"Nat. Biotechnol"},{"key":"B124","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.ophtha.2018.04.001","article-title":"Clustered regularly interspaced short palindromic repeats-based genome surgery for the treatment of autosomal dominant retinitis pigmentosa","volume":"125","author":"Tsai","year":"2018","journal-title":"Ophthalmology"},{"key":"B125","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.survophthal.2010.08.002","article-title":"Photodynamic therapy of choroidal hemangioma in sturge-weber syndrome, with a review of treatments for diffuse and circumscribed choroidal hemangiomas","volume":"56","author":"Tsipursky","year":"2011","journal-title":"Surv. Ophthalmol"},{"key":"B126","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/s0002-9394(01)00967-9","article-title":"Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization\u2013verteporfin in photodynamic therapy report 2","volume":"131","year":"2001","journal-title":"Am. J. Ophthalmol"},{"key":"B127","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/s41591-018-0204-6","article-title":"High prevalence of Streptococcus pyogenes Cas9-reactive T cells within the adult human population","volume":"25","author":"Wagner","year":"2019","journal-title":"Nat. Med"},{"key":"B128","doi-asserted-by":"publisher","first-page":"249","DOI":"10.2165\/00003495-200060020-00002","article-title":"Viral vectors for gene transfer","volume":"60","author":"Walther","year":"2000","journal-title":"Drugs"},{"key":"B129","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/j.ajpath.2013.05.011","article-title":"Short hairpin RNA-mediated knockdown of VEGFA in M\u00fcller cells reduces intravitreal neovascularization in a rat model of retinopathy of prematurity","volume":"183","author":"Wang","year":"2013","journal-title":"Am. J. Pathol"},{"key":"B130","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.2337\/db09-1420","article-title":"M\u00fcller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage","volume":"59","author":"Wang","year":"2010","journal-title":"Diabetes"},{"key":"B131","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1089\/hum.2017.179","article-title":"Assessment of adeno-associated virus serotype tropism in human retinal explants","volume":"29","author":"Wiley","year":"2018","journal-title":"Hum. Gene Ther"},{"key":"B132","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ajo.2017.11.020","article-title":"Choroidal changes after suprachoroidal injection of triamcinolone acetonide in eyes with macular edema secondary to retinal vein occlusion","volume":"186","author":"Willoughby","year":"2018","journal-title":"Am. J. Ophthalmol"},{"key":"B133","doi-asserted-by":"publisher","first-page":"6082","DOI":"10.1167\/iovs.17-21902","article-title":"AAV-CRISPR\/Cas9\u2013mediated depletion of VEGFR2 blocks angiogenesis in vitro","volume":"58","author":"Wu","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B134","doi-asserted-by":"publisher","first-page":"e3000747","DOI":"10.1371\/journal.pbio.3000747","article-title":"High-fidelity SaCas9 identified by directional screening in human cells","volume":"18","author":"Xie","year":"2020","journal-title":"PLoS Biol"},{"key":"B135","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/nm1365","article-title":"Effective gene therapy with nonintegrating lentiviral vectors","volume":"12","author":"Y\u00e1\u00f1ez-Mu\u00f1oz","year":"2006","journal-title":"Nat. Med"},{"key":"B136","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1016\/j.ophtha.2020.01.006","article-title":"Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis","volume":"127","author":"Yeh","year":"2020","journal-title":"Ophthalmology"},{"key":"B137","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.oret.2017.09.015","article-title":"Genome editing in retinal diseases using CRISPR technology","volume":"2","author":"Yiu","year":"2018","journal-title":"Ophthalmol. Retina"},{"key":"B138","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.omtm.2020.01.002","article-title":"Suprachoroidal and subretinal injections of AAV using transscleral microneedles for retinal gene delivery in nonhuman primates","volume":"16","author":"Yiu","year":"","journal-title":"Mol. Ther. Methods Clin. Dev"},{"key":"B139","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1167\/iovs.61.2.32","article-title":"Long-term evolution and remodeling of soft drusen in rhesus macaques","volume":"61","author":"Yiu","year":"","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B140","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.ajo.2014.06.006","article-title":"Effect of anti-vascular endothelial growth factor therapy on choroidal thickness in diabetic macular edema","volume":"158","author":"Yiu","year":"2014","journal-title":"Am. J. Ophthalmol"},{"key":"B141","doi-asserted-by":"publisher","first-page":"5490","DOI":"10.1167\/iovs.16-20296","article-title":"Genomic disruption of VEGF-a expression in human retinal pigment epithelial cells using CRISPR-Cas9 endonuclease","volume":"57","author":"Yiu","year":"2016","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B142","doi-asserted-by":"publisher","first-page":"5049","DOI":"10.1038\/s41598-019-41509-2","article-title":"Vascular response to sildenafil citrate in aging and age-related macular degeneration","volume":"9","author":"Yiu","year":"2019","journal-title":"Sci. Rep"},{"key":"B143","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.oret.2019.08.009","article-title":"Spectral-domain OCT predictors of visual outcomes after ranibizumab treatment for macular edema resulting from retinal vein occlusion","volume":"4","author":"Yiu","year":"","journal-title":"Ophthalmol. Retina"},{"key":"B144","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1038\/s41467-019-09005-3","article-title":"A gRNA-tRNA array for CRISPR-Cas9 based rapid multiplexed genome editing in saccharomyces cerevisiae","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat. Commun"},{"key":"B145","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1093\/nsr\/nwaa033","article-title":"CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration","volume":"7","author":"Zhou","year":"2020","journal-title":"Natl. Sci. Rev"},{"key":"B146","doi-asserted-by":"publisher","first-page":"549412","DOI":"10.1155\/2015\/549412","article-title":"Hypoxia-inducible factor-1 in physiological and pathophysiological angiogenesis: applications and therapies","volume":"2015","author":"Zimna","year":"2015","journal-title":"BioMed Res. Int"},{"key":"B147","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/nbt.3081","article-title":"Efficient delivery of genome-editing proteins in vitro and in vivo","volume":"33","author":"Zuris","year":"2015","journal-title":"Nat. Biotechnol"}],"container-title":["Frontiers in Genome Editing"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgeed.2020.594984\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T08:55:28Z","timestamp":1608627328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgeed.2020.594984\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,22]]},"references-count":147,"alternative-id":["10.3389\/fgeed.2020.594984"],"URL":"https:\/\/doi.org\/10.3389\/fgeed.2020.594984","relation":{},"ISSN":["2673-3439"],"issn-type":[{"value":"2673-3439","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,22]]},"article-number":"594984"}}