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CRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization

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dc.contributor.author변석호-
dc.contributor.author이준원-
dc.contributor.author곽지용-
dc.date.accessioned2023-04-20T08:33:42Z-
dc.date.available2023-04-20T08:33:42Z-
dc.date.issued2023-03-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/194119-
dc.description.abstractThe CRISPR/Cas9 system easily edits target genes in various organisms and is used to treat human diseases. In most therapeutic CRISPR studies, ubiquitously expressed promoters, such as CMV, CAG, and EF1α, are used; however, gene editing is sometimes necessary only in specific cell types relevant to the disease. Therefore, we aimed to develop a retinal pigment epithelium (RPE)-specific CRISPR/Cas9 system. We developed a CRISPR/Cas9 system that operates only in retinal pigment epithelium (RPE) by expressing Cas9 under the RPE-specific vitelliform macular dystrophy 2 promoter (pVMD2). This RPE-specific CRISPR/pVMD2-Cas9 system was tested in human retinal organoid and mouse model. We confirmed that this system works specifically in the RPE of human retinal organoids and mouse retina. In addition, the RPE-specific Vegfa ablation using the novel CRISPR-pVMD2-Cas9 system caused regression of choroidal neovascularization (CNV) without unwanted knock-out in the neural retina in laser-induced CNV mice, which is a widely used animal model of neovascular age-related macular degeneration. RPE-specific Vegfa knock-out (KO) and ubiquitous Vegfa KO were comparable in the efficient regression of CNV. The promoter substituted, cell type-specific CRISPR/Cas9 systems can be used in specific 'target cell' therapy, which edits genes while reducing unwanted off- 'target cell' effects. © 2023. The Author(s).-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherNature Publishing Group-
dc.relation.isPartOfSCIENTIFIC REPORTS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHCRISPR-Cas Systems-
dc.subject.MESHChoroidal Neovascularization* / genetics-
dc.subject.MESHChoroidal Neovascularization* / therapy-
dc.subject.MESHCraniocerebral Trauma*-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHRetina-
dc.subject.MESHRetinal Pigment Epithelium-
dc.subject.MESHVascular Endothelial Growth Factor A / genetics-
dc.titleCRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Ophthalmology (안과학교실)-
dc.contributor.googleauthorJinkyu Park-
dc.contributor.googleauthorGang Cui-
dc.contributor.googleauthorHyundong Lee-
dc.contributor.googleauthorHan Jeong-
dc.contributor.googleauthorJay Jiyong Kwak-
dc.contributor.googleauthorJunwon Lee-
dc.contributor.googleauthorSuk Ho Byeon-
dc.identifier.doi10.1038/s41598-023-29014-z-
dc.contributor.localIdA01849-
dc.contributor.localIdA03179-
dc.relation.journalcodeJ02646-
dc.identifier.eissn2045-2322-
dc.identifier.pmid36878916-
dc.contributor.alternativeNameByeon, Suk Ho-
dc.contributor.affiliatedAuthor변석호-
dc.contributor.affiliatedAuthor이준원-
dc.citation.volume13-
dc.citation.number1-
dc.citation.startPage3715-
dc.identifier.bibliographicCitationSCIENTIFIC REPORTS, Vol.13(1) : 3715, 2023-03-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers

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