Application of virus-mediated gene transduction technology in ophthalmology research_Chinese Journal of Ocular Fundus Diseases

Authors：

Dong Lijie , Zhang Hui , Wang Qiong , Hong Yaru ,  Li Xiaorong

Tianjin Medical University Hospital, Tianjin Medical University Eye Institute, School of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China;

Corresponding author：

Li Xiaorong, Email: xiaorli@163.com

Keywords：

Gene transfer, horizontal; Review; Viral vector

DOI：

10.3760/cma.j.issn.1005-1015.2020.02.019

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

With the advancement of molecular biology technology and the development of genetics, the viral vector system has been continuously improved and optimized. The viral vector system has gradually become one of the best carriers in ophthalmic gene therapy. Adenovirus vector has the characteristics of transient expression and plays an important role in reducing corneal immune response. Lentiviral vector has the characteristics of stable and high efficiency and can be expressed slowly in the body for a long time.Adeno-associated virus vector has the characteristics of low immunogenicity, high efficiency and precision and can infect a variety of retinal cells. The combined use of adeno-associated virus vector and CRISPR-Cas9 provides new methods for precise treatment of ophthalmic genetic diseases. The advent of viral vectors has significantly increased the potential of gene therapy and has unparalleled advantages over traditional therapies. We have reason to believe that virus-based gene transduction technology will soon achieve clinical application in the near future, and a large number of difficult ophthalmic problems will be solved by then.

Citation： Dong Lijie, Zhang Hui, Wang Qiong, Hong Yaru, Li Xiaorong. Application of virus-mediated gene transduction technology in ophthalmology research. Chinese Journal of Ocular Fundus Diseases, 2020, 36(2): 165-170. doi: 10.3760/cma.j.issn.1005-1015.2020.02.019 Copy

1.	Kalesnykas G, Kokki E, Alasaarela L, et al. Comparative study of adeno-associated virus, adenovirus, bacu lovirus and lentivirus vectors for gene therapy of the eyes[J]. Curr Gene Ther, 2017, 17(3): 235-247. DOI: 10.2174/1566523217666171003170348.
2.	田芳, 东莉洁, 周玉, 等. 重组腺相关病毒-多聚嘧啶序列结合蛋白相关剪接因子对氧诱导视网膜新生血管形成的抑制作用[J]. 中华眼底病杂志, 2014, 30(5): 504-508. DOI: 10.3760/cma.j.issn.1005-1015.2014.05.019.Tian F, Dong LJ, Zhou Y, et al. Inhibition of oxygen induced retinal neovascularization by recombinant adeno-associated virus-polypyrimidine tract-binding protein-associated splicing factor intraocular injection in mice[J]. Chin J Ocul Fundus Dis, 2014, 30(5): 504-508. DOI: 10.3760/cma.j.issn.1005-1015.2014.05.019.
3.	田芳, 东莉洁, 吉洁, 等. 多聚嘧啶序列结合蛋白相关剪接因子对视网膜血管内皮细胞IGF-1/VEGF信号通路的抑制作用[J]. 中华实验眼科杂志, 2016, 34(1): 11-16. DOI: 10.3760/cma.j.issn.2095-0160.2016.01.003.Tian F, Dong LJ, Ji J, et al. Inhibition of PTB-associated splicing factor on IGF-1/VEGF signaling pathway in retinal vascular endothelial cells[J]. Chin J Exp Ophthalmol, 2016, 34(1): 11-16. DOI: 10.3760/cma.j.issn.2095-0160.2016.01.003.
4.	漆晨, 张慧, 林婷婷, 等. 聚嘧啶束结合蛋白相关剪接因子高表达对糖基化终末产物诱导下视网膜色素上皮细胞损伤的保护作用[J]. 中华眼底病杂志, 2020, 36(1): 46-52. DOI: 10.3760/cma.j.issn.1005-1015.2020.01.011.Qi C, Zhang H, Lin TT, et al. Protective effect of polypyrimidine bundle-binding protein-related splicing factor on retinal pigment epithelial cell injury induced by advanced glycation end products[J]. Chin J Ocul Fundus Dis, 2020, 36(1): 46-52. DOI: 10.3760/cma.j.issn.1005-1015.2020.01.011.
5.	漆晨, 东莉洁, 乐毅, 等. 多聚嘧啶序列结合蛋白相关剪接因子对体外培养的视网膜色素上皮细胞磷脂酰肌醇3激酶/丝氨酸-苏氨酸蛋白激酶信号通路的调控作用[J]. 中华眼底病杂志, 2015, 31(4): 363-367. DOI: 10.3760/cma.j.issn.1005-1015.2015.04.013.Qi C, Dong LJ, Yue Y, et al. The regulation of PTB-associated splicing factor on phosphatidylinositol 3 kinase/Akt signaling pathway in retinal pigment epithelial cells[J]. Chin J Ocul Fundus Dis, 2015, 31(4): 363-367. DOI: 10.3760/cma.j.issn.1005-1015.2015.04.013.
6.	田芳, 李文博, 黄亮瑜, 等. 聚嘧啶束结合蛋白相关剪接因子对过氧化氢诱导下视网膜色素上皮细胞凋亡的影响[J]. 中华眼底病杂志, 2018, 34(2): 159-163. DOI: 10.3760/cma.j.issn.1005-1015.2018.02.012.Tian F, Li WB, Huang LY, et al. The effect of polypyrimidine tract binding protein-associated splicing factor on hydrogen peroxide induced apoptosis of retinal pigment epithelial[J]. Chin J Ocul Fundus Dis, 2018, 34(2): 159-163. DOI: 10.3760/cma.j.issn.1005-1015.2018.02.012.
7.	田芳, 胡博杰, 李文博, 等. 高表达多聚嘧啶序列结合蛋白相关剪接因子对糖基化终产物诱导下视网膜Müller细胞凋亡的影响[J]. 中华眼底病杂志, 2019, 35(1): 70-75. DOI: 10.3760/cma.j.issn.1005-1015.2019.01.015.Tian F, Hu BJ, Li WB, et al. Effects of polypyramidine tract binding protein-associated splicing factor overexpression on apoptosis of human Müller cells under advanced glycation end products treatment[J]. Chin J Ocul Fundus Dis, 2019, 35(1): 70-75. DOI: 10.3760/cma.j.issn.1005-1015.2019.01.015.
8.	Shi L, Guo H, Li Z, et al. Adenovirus-mediated down-regulation of miR-21-5p alleviates experimental autoimmune uveoretinitis in mice[J/OL]. Int Immunopharmacol, 2019, 74: 105698[2019-09-01]. https://www.sciencedirect.com/science/article/pii/S1567576919300566. DOI: 10.1016/j.intimp.2019.105698.
9.	Kokki E, Karttunen T, Olsson V, et al. Human vascular endothelial growth factor A165 expression induces the mouse model of neovascular age-related macular degeneration[J/OL]. Genes, 2018, 9(9): 438[2018-08-31]. https://www.mdpi.com/2073-4425/9/9/438. DOI: 10.3390/genes9090438.
10.	Nagayasu K. The biological basis and application of lentiviral vector and adeno-associated viral vector in pharmacological research[J]. Nihon Yakurigaku Zasshi, 2019, 153(5): 204-209. DOI: 10.1254/fpj.153.204.
11.	Bai L, Liang W, Chen M, et al. Effect of lentivirus-mediated gene silencing, targeting toll-like receptor 2, on corneal allograft transplantation in rats[J]. Mol Immunol, 2017, 91: 97-104. DOI: 10.1016/j.molimm.2017.08.022.
12.	黄亮瑜, 柯屹峰, 林婷婷, 等. 慢病毒介导聚嘧啶束结合蛋白相关剪接因子对氧诱导视网膜病变小鼠视网膜新生血管的抑制作用[J]. 中华眼底病杂志, 2020, 36(1): 53-59. DOI: 10.3760/cma.j.issn.1005-1015.2020.01.012.Huang LY, Ke YF, Lin TT, et al. Lentivirus-mediated polypyrimidine bundle binding protein-associated splicing factor inhibits retinal neovascularization in mice of oxygen-induced retinopathy[J]. Chin J Ocul Fundus Dis, 2020, 36(1): 53-59. DOI: 10.3760/cma.j.issn.1005-1015.2020.01.012.
13.	牛瑞, 东莉洁, 马腾, 等. 结缔组织生长因子重组干扰载体慢病毒颗粒的构建及其对视网膜血管内皮细胞内源性结缔组织生长因子表达的抑制作用[J]. 中华眼底病杂志, 2018, 34(6): 580-585. DOI: 10.3760/cma.j.issn.1005-1015.2018.06.011.Niu R, Dong LJ, Ma T, et al. Construction of connective tissue growth factor recombinant interference vector lentiviral particle and its inhibitory effect on endogenous connective tissue growth factor expression in retinal vascular endothelial cells[J]. Chin J Ocul Fundus Dis, 2018, 34(6): 580-585. DOI: 10.3760/cma.j.issn.1005-1015.2018.06.011.
14.	Sun YY, Yang YF, Keller KE. Myosin-X silencing in the trabecular meshwork suggests a role for tunneling nanotubes in outflow regulation[J]. Invest Ophthalmol Vis Sci, 2019, 60(2): 843-851. DOI: 10.1167/iovs.18-26055.
15.	Rivera VM, Gao GP, Grant RL, et al. Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer[J]. Blood, 2005, 105(4): 1424-1430. DOI: 10.1182/blood-2004-06-2501.
16.	Lee SH, Kim YS, Nah SK, et al. Transduction patterns of adeno-associated viral vectors in a laser-induced choroidal neovascularization mouse model[J]. Mol Ther Methods Clin Dev, 2018, 9: 90-98. DOI: 10.1016/j.omtm.2018.01.008.
17.	Brydon EM, Bronstein R, Buskin A, et al. AAV-mediated gene augmentation therapy restores critical functions in mutant PRPF31^+/- iPSC-derived RPE cells[J]. Mol Ther Methods Clin Dev, 2019, 15: 392-402. DOI: 10.1016/j.omtm.2019.10.014.
18.	Quinn PM, Buck TM, Mulder AA, et al. Human iPSC-derived retinas recapitulate the fetal CRB1 CRB2 complex formation and demonstrate that photoreceptors and muller glia are targets of AAV5[J]. Stem Cell Reports, 2019, 12(5): 906-919. DOI: 10.1016/j.stemcr.2019.03.002.
19.	Basche M, Kampik D, Kawasaki S, et al. Sustained and widespread gene delivery to the corneal epithelium via in situ transduction of limbal epithelial stem cells, using lentiviral and adeno-associated viral vectors[J]. Hum Gene Ther, 2018, 29(10): 1140-1152. DOI: 10.1089/hum.2018.115.
20.	Manghwar H, Lindsey K, Zhang X, et al. CRISPR/Cas system: recent advances and future prospects for genome editing[J]. Trends Plant Sci, 2019, 24(12): 1102-1125. DOI: 10.1016/j.tplants.2019.09.006.
21.	Lau CH, Suh Y. In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease[J]. F1000Res, 2017, 6: 2153. DOI: 10.12688/f1000research.11243.1.
22.	Hung SS, Chrysostomou V, Li F, et al. AAV-mediated CRISPR/Cas gene editing of retinal cells in vivo[J]. Invest Ophthalmol Vis Sci, 2016, 57(7): 3470-3476. DOI: 10.1167/iovs.16-19316.
23.	Yu W, Wu Z. Use of AAV vectors for CRISPR-mediated in vivo genome editing in the retina[J]. Methods Mol Biol, 2019, 1950: 123-139. DOI: 10.1007/978-1-4939-9139-6_7.
24.	Cheng G, Tian K, Zhang L, et al. S100A4 gene silencing in oxygen-induced ischemic retinopathy inhibits retinal neovascularization via down-regulation of CREB expression[J]. Graefe’s Arch Clin Exp Ophthalmol, 2016, 254(1): 97-108. DOI: 10.1007/s00417-015-3158-0.
25.	Li J, Wang JJ, Zhang SX. NADPH oxidase 4-derived H₂O₂ promotes aberrant retinal neovascularization via activation of VEGF receptor 2 pathway in oxygen-induced retinopathy[J/OL]. J Diabetes Res, 2015, 2015: 963289[2015-03-18]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381975/. DOI: 10.1155/2015/963289.
26.	Han J, Li N. Adenoviral vector-mediated delivery of p21WAF1/CIP1 prevents retinal neovascularization in an oxygen-induced retinopathy model[J]. Curr Eye Res, 2016, 41(8): 1113-1117. DOI: 10.3109/02713683.2015.1090002.
27.	Wang QM, Zhao XY, Zhi W, et al. IL-10 modified immature dendritic cells attenuate immune rejection in a rat model of high-risk corneal transplantation[J]. J Biomater Tiss Eng, 2017, 7(5): 408-412. DOI: 10.1166/jbt.2017.1578.
28.	Kaufmann C, Mortimer LA, Brereton HM, et al. Interleukin-10 gene transfer in rat limbal transplantation[J]. Curr Eye Res, 2017, 42(11): 1426-1434. DOI: 10.1080/02713683.2017.1344714.
29.	李汉林, 谷晋, 周琼, 等. 腺病毒载体介导血管抑素防治兔高危角膜移植术后新生血管化的实验研究[J]. 江西医药, 2012, 47(2): 115-117. DOI: 10.3969/j.issn.1006-2238.2012.02.010.Li HL, Gu J, Zhou Q. Effects of recombinant adenovirus-mediated angiostatin on inhibiting high-risk keratoplasty neovascularization of rabbit[J]. Jiangxi Medical Journal, 2012, 47(2): 115-117. DOI: 10.3969/j.issn.1006-2238.2012.02.010.
30.	Serratrice N, Cubizolle A, Ibanes S, et al. Corrective GUSB transfer to the canine mucopolysaccharidosis Ⅶ cornea using a helper-dependent canine adenovirus vector[J]. J Control Release, 2014, 181: 22-31. DOI: 10.1016/j.jconrel.2014.02.022.
31.	Loewen N, Fautsch MP, Teo WL, et al. Long-term, targeted genetic modification of the aqueous humor outflow tract coupled with noninvasive imaging of gene expression in vivo[J]. Invest Ophthalmol Vis Sci, 2004, 45(9): 3091-3098. DOI: 10.1167/iovs.04-0366.
32.	Aktas Z, Rao H, Slauson SR, et al. Proteasome inhibition increases the efficiency of lentiviral vector-mediated transduction of trabecular meshwork[J]. Invest Ophthalmol Vis Sci, 2018, 59(1): 298-310. DOI: 10.1167/iovs.17-22074.
33.	Sun W, Li YN, Ye JF, et al. MEG3 is involved in the development of glaucoma through promoting the autophagy of retinal ganglion cells[J]. Eur Rev Med Pharmacol Sci, 2018, 22(9): 2534-2540. DOI: 10.26355/eurrev_201805_14942.
34.	Song WT, Zhang XY, Xia XB. Atoh7 promotes the differentiation of muller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma[J]. Exp Biol Med (Maywood), 2015, 240(5): 682-690. DOI: 10.1177/1535370214560965.
35.	He Y, Li HB, Li X, et al. MiR-124 promotes the growth of retinal ganglion cells derived from muller cells[J]. Cell Physiol Biochem, 2018, 45(3): 973-983. DOI: 10.1159/000487292.
36.	Tan J, Liu G, Zhu X, et al. Lentiviral vector-mediated expression of exoenzyme C3 transferase lowers intraocular pressure in monkeys[J]. Mol Ther, 2019, 27(7): 1327-1338. DOI: 10.1016/j.ymthe.2019.04.021.
37.	田芳, 赵今稚, 黄亮瑜, 等. 高表达Krüppel样因子6对紫外线B诱导的人晶状体上皮细胞凋亡的影响[J]. 中华实验眼科杂志, 2019, 37(4): 257-262. DOI: 10.3760/cma.j.issn.2095-0160.2019.04.004.Tian F, Zhao JZ, Huang LY, et al. Effects of Krüppel-like factor 6 overexpression towards apoptosis of human lens epithelial cells with ultra violetradiation B treatment[J]. Chin J Exp Ophthalmol, 2019, 37(4): 257-262. DOI: 10.3760/cma.j.issn.2095-0160.2019.04.004.
38.	田芳, 赵今稚, 滕贺, 等. Krüppel样因子6经活化转录因子4通路对晶状体上皮细胞凋亡的调控作用[J]. 中华实验眼科杂志, 2018, 36(3): 181-186. DOI: 10.3760/cma.j.issn.2095-0160.2018.03.005.Tian F, Zhao JZ, Teng H, et al. Regulation of Krüppel-like factor 6 via activating transcription factor 4 pathway to apoptosis of human lens epithelial cells[J]. Chin J Exp Ophthalmol, 2018, 36(3): 181-186. DOI: 10.3760/cma.j.issn.2095-0160.2018.03.005.
39.	高美子, 黄亮瑜, 东莉洁, 等. Krüppel样因子6对于TGF-β1诱导的晶状体上皮细胞纤维化的调控作用研究[J]. 中国中医眼科杂志, 2018, 28(1): 4-11. DOI: 10.13444/j.cnki.zgzyykzz.2018.01.002.Gao MZ, Huang LY, Dong LJ, et al. Regulation of Krüppel-like Factor 6 on TGF-β1-induced fibrosis of lens epithelial cells[J]. Chinese Journal of Chinese Ophthalmology, 2018, 28(1): 4-11. DOI: 10.13444/j.cnki.zgzyykzz.2018.01.002.
40.	滕贺, 黄亮瑜, 田芳, 等. 衰老标记蛋白30高表达对紫外线诱导人晶状体上皮细胞凋亡的影响[J]. 中华眼科杂志, 2017, 53(11): 835-841. DOI: 10.3760/cma.j.issn.0412-4081.2017.11.007.Teng H, Huang LY, Tian F, et al. Effects of SMP-30 overexpression on apoptosis of human lens epithelial cells induced by ultraviolet B irradiation[J]. Chin J Ophthalmol, 2017, 53(11): 835-841. DOI: 10.3760/cma.j.issn.0412-4081.2017.11.007.
41.	刘勃实, 东莉洁, 李筱荣, 等. 慢病毒介导的微小RNA-191对小鼠视网膜新生血管的抑制作用[J]. 中华眼底病杂志, 2019, 35(5): 475-479. DOI: 10.3760/cma.j.issn.1005-1015.2019.05.010.Liu BS, Dong LJ, Li XR, et al. miR-191 inhibits oxygen-induced retinal neovascularization in mice[J]. Chin J Ocul Fundus Dis, 2019, 35(5): 475-479. DOI: 10.3760/cma.j.issn.1005-1015.2019.05.010.
42.	Pang JJ, Chang B, Kumar A, et al. Gene therapy restores vision-dependent behavior as well as retinal structure and function in a mouse model of rpe65 leber congenital amaurosis[J]. Mol Ther, 2006, 13(3): 565-572. DOI: 10.1016/j.ymthe.2005.09.001.
43.	Acland GM, Aguirre GD, Bennett J, et al. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness[J]. Mol Ther, 2005, 12(6): 1072-1082. DOI: 10.1016/j.ymthe.2005.08.008.
44.	Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial[J]. Lancet, 2009, 374(9701): 1597-1605. DOI: 10.1016/s0140-6736(09)61836-5.
45.	Bennett J, Wellman J, Marshall KA, et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial[J]. Lancet, 2016, 388(10045): 661-672. DOI: 10.1016/s0140-6736(16)30371-3.
46.	Bennett J, Ashtari M, Wellman J, et al. AAV2 gene therapy readministration in three adults with congenital blindness[J/OL]. Sci Transl Med, 2012, 4(120): 120ra115[2012-02-01]. https://www.researchgate.net/publication/221822316_AAV2_Gene_Therapy_Readministration_in_Three_Adults_with_Congenital_Blindness. DOI: 10.1126/scitranslmed.3002865.
47.	Maguire AM, Russell S, Wellman JA, et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials[J]. Ophthalmology, 2019, 126(9): 1273-1285. DOI: 10.1016/j.ophtha.2019.06.017.
48.	Lai CM, Shen WY, Brankov M, et al. Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys[J]. Mol Ther, 2005, 12(4): 659-668. DOI: 10.1016/j.ymthe.2005.04.022.
49.	Rakoczy EP, Magno AL, Lai CM, et al. Three-year follow-up of phase 1 and 2a rAAV. sFLT-1 subretinal gene therapy trials for exudative age-related macular degeneration[J]. Am J Ophthalmol, 2019, 204: 113-123. DOI: 10.1016/j.ajo.2019.03.006.
50.	Heier JS, Kherani S, Desai S, et al. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial[J]. Lancet, 2017, 390(10089): 50-61. DOI: 10.1016/s0140-6736(17)30979-0.
51.	Taylor RL, Poulter JA, Downes SM, et al. Loss-of-function mutations in the CFH gene affecting alternatively encoded factor H-like 1 protein cause dominant early-onset macular drusen[J]. Ophthalmology, 2019, 126(10): 1410-1421. DOI: 10.1016/j.ophtha.2019.03.013.
52.	Schnabolk G, Parsons N, Obert E, et al. Delivery of CR2-fH using aav vector therapy as treatment strategy in the mouse model of choroidal neovascularization[J]. Mol Ther Methods Clin Dev, 2018, 9: 1-11. DOI: 10.1016/j.omtm.2017.11.003.
53.	Kwong JM, Gu L, Nassiri N, et al. AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury[J]. Gene Ther, 2015, 22(2): 138-145. DOI: 10.1038/gt.2014.105.
54.	刘爱华, 高美子, 黄亮瑜, 等. 叉头框转录因子F2小发夹RNA对人眼小梁网细胞外基质蛋白表达的抑制作用[J]. 中华实验眼科杂志, 2019, 37(6): 405-410. DOI: 10.3760/cma.j.issn.2095-0160.2019.06.002.Liu AH, Gao MZ, Huang LY, et al. The inhibitory effect of FoxF2 shRNA on the expression of extracellular matrix of human trabecular meshwork[J]. Chin J Exp Ophthalmol, 2019, 37(6): 405-410. DOI: 10.3760/cma.j.issn.2095-0160.2019.06.002.
55.	Buie LK, Rasmussen CA, Porterfield EC, et al. Self-complementary AAV virus (scAAV) safe and long-term gene transfer in the trabecular meshwork of living rats and monkeys[J]. Invest Ophthalmol Vis Sci, 2010, 51(1): 236-248. DOI: 10.1167/iovs.09-3847.
56.	Bogner B, Boye SL, Min SH, et al. Capsid mutated adeno-associated virus delivered to the anterior chamber results in efficient transduction of trabecular meshwork in mouse and rat[J/OL]. PLoS One, 2015, 10(6): 0128759[2015-06-08]. hhttps://core.ac.uk/display/89605988. DOI: 10.1371/journal.pone.0128759.
57.	Wang L, Xiao R, Andres-Mateos E, et al. Single stranded adeno-associated virus achieves efficient gene transfer to anterior segment in the mouse eye[J/OL]. PLoS One. 2017, 12(8): 0182473[2017-08-01]. http://adsabs.harvard.edu/abs/2017PLoSO..1282473W. DOI: 10.1371/journal.pone.0182473.
58.	O'Callaghan J, Crosbie DE, Cassidy PS, et al. Therapeutic potential of AAV-mediated MMP-3 secretion from corneal endothelium in treating glaucoma[J]. Hum Mol Genet, 2017, 26(7): 1230-1246. DOI: 10.1093/hmg/ddx028.
59.	Fu X, Huu VAN, Duan Y, et al. Clinical applications of retinal gene therapies[J]. Pre Clin Med, 2018, 1(1): 5-20. DOI: 10.1093/pcmedi/pby004.
60.	Zhu J, Ming C, Fu X, et al. Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors[J]. Cell Res, 2017, 27(6): 830-833. DOI: 10.1038/cr.2017.57.
61.	Yu W, Mookherjee S, Chaitankar V, et al. Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice[J/OL]. Nat Commun, 2017, 8: 14716[2017-03-14]. https://www.nature.com/articles/ncomms14716. DOI: 10.1038/ncomms14716.
62.	Suzuki K, Tsunekawa Y, Hernandez-Benitez R, et al. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration[J]. Nature, 2016, 540(7631): 144-149. DOI: 10.1038/nature20565.
63.	McCullough KT, Boye SL, Fajardo D, et al. Somatic gene editing of GUCY2D by AAV-CRISPR/Cas9 alters retinal structure and function in mouse and macaque[J]. Hum Gene Ther, 2019, 30(5): 571-589. DOI: 10.1089/hum.2018.193.

1. Kalesnykas G, Kokki E, Alasaarela L, et al. Comparative study of adeno-associated virus, adenovirus, bacu lovirus and lentivirus vectors for gene therapy of the eyes[J]. Curr Gene Ther, 2017, 17(3): 235-247. DOI: 10.2174/1566523217666171003170348.
2. 田芳, 东莉洁, 周玉, 等. 重组腺相关病毒-多聚嘧啶序列结合蛋白相关剪接因子对氧诱导视网膜新生血管形成的抑制作用[J]. 中华眼底病杂志, 2014, 30(5): 504-508. DOI: 10.3760/cma.j.issn.1005-1015.2014.05.019.Tian F, Dong LJ, Zhou Y, et al. Inhibition of oxygen induced retinal neovascularization by recombinant adeno-associated virus-polypyrimidine tract-binding protein-associated splicing factor intraocular injection in mice[J]. Chin J Ocul Fundus Dis, 2014, 30(5): 504-508. DOI: 10.3760/cma.j.issn.1005-1015.2014.05.019.
3. 田芳, 东莉洁, 吉洁, 等. 多聚嘧啶序列结合蛋白相关剪接因子对视网膜血管内皮细胞IGF-1/VEGF信号通路的抑制作用[J]. 中华实验眼科杂志, 2016, 34(1): 11-16. DOI: 10.3760/cma.j.issn.2095-0160.2016.01.003.Tian F, Dong LJ, Ji J, et al. Inhibition of PTB-associated splicing factor on IGF-1/VEGF signaling pathway in retinal vascular endothelial cells[J]. Chin J Exp Ophthalmol, 2016, 34(1): 11-16. DOI: 10.3760/cma.j.issn.2095-0160.2016.01.003.
4. 漆晨, 张慧, 林婷婷, 等. 聚嘧啶束结合蛋白相关剪接因子高表达对糖基化终末产物诱导下视网膜色素上皮细胞损伤的保护作用[J]. 中华眼底病杂志, 2020, 36(1): 46-52. DOI: 10.3760/cma.j.issn.1005-1015.2020.01.011.Qi C, Zhang H, Lin TT, et al. Protective effect of polypyrimidine bundle-binding protein-related splicing factor on retinal pigment epithelial cell injury induced by advanced glycation end products[J]. Chin J Ocul Fundus Dis, 2020, 36(1): 46-52. DOI: 10.3760/cma.j.issn.1005-1015.2020.01.011.
5. 漆晨, 东莉洁, 乐毅, 等. 多聚嘧啶序列结合蛋白相关剪接因子对体外培养的视网膜色素上皮细胞磷脂酰肌醇3激酶/丝氨酸-苏氨酸蛋白激酶信号通路的调控作用[J]. 中华眼底病杂志, 2015, 31(4): 363-367. DOI: 10.3760/cma.j.issn.1005-1015.2015.04.013.Qi C, Dong LJ, Yue Y, et al. The regulation of PTB-associated splicing factor on phosphatidylinositol 3 kinase/Akt signaling pathway in retinal pigment epithelial cells[J]. Chin J Ocul Fundus Dis, 2015, 31(4): 363-367. DOI: 10.3760/cma.j.issn.1005-1015.2015.04.013.
6. 田芳, 李文博, 黄亮瑜, 等. 聚嘧啶束结合蛋白相关剪接因子对过氧化氢诱导下视网膜色素上皮细胞凋亡的影响[J]. 中华眼底病杂志, 2018, 34(2): 159-163. DOI: 10.3760/cma.j.issn.1005-1015.2018.02.012.Tian F, Li WB, Huang LY, et al. The effect of polypyrimidine tract binding protein-associated splicing factor on hydrogen peroxide induced apoptosis of retinal pigment epithelial[J]. Chin J Ocul Fundus Dis, 2018, 34(2): 159-163. DOI: 10.3760/cma.j.issn.1005-1015.2018.02.012.
7. 田芳, 胡博杰, 李文博, 等. 高表达多聚嘧啶序列结合蛋白相关剪接因子对糖基化终产物诱导下视网膜Müller细胞凋亡的影响[J]. 中华眼底病杂志, 2019, 35(1): 70-75. DOI: 10.3760/cma.j.issn.1005-1015.2019.01.015.Tian F, Hu BJ, Li WB, et al. Effects of polypyramidine tract binding protein-associated splicing factor overexpression on apoptosis of human Müller cells under advanced glycation end products treatment[J]. Chin J Ocul Fundus Dis, 2019, 35(1): 70-75. DOI: 10.3760/cma.j.issn.1005-1015.2019.01.015.
8. Shi L, Guo H, Li Z, et al. Adenovirus-mediated down-regulation of miR-21-5p alleviates experimental autoimmune uveoretinitis in mice[J/OL]. Int Immunopharmacol, 2019, 74: 105698[2019-09-01]. https://www.sciencedirect.com/science/article/pii/S1567576919300566. DOI: 10.1016/j.intimp.2019.105698.
9. Kokki E, Karttunen T, Olsson V, et al. Human vascular endothelial growth factor A165 expression induces the mouse model of neovascular age-related macular degeneration[J/OL]. Genes, 2018, 9(9): 438[2018-08-31]. https://www.mdpi.com/2073-4425/9/9/438. DOI: 10.3390/genes9090438.
10. Nagayasu K. The biological basis and application of lentiviral vector and adeno-associated viral vector in pharmacological research[J]. Nihon Yakurigaku Zasshi, 2019, 153(5): 204-209. DOI: 10.1254/fpj.153.204.
11. Bai L, Liang W, Chen M, et al. Effect of lentivirus-mediated gene silencing, targeting toll-like receptor 2, on corneal allograft transplantation in rats[J]. Mol Immunol, 2017, 91: 97-104. DOI: 10.1016/j.molimm.2017.08.022.
12. 黄亮瑜, 柯屹峰, 林婷婷, 等. 慢病毒介导聚嘧啶束结合蛋白相关剪接因子对氧诱导视网膜病变小鼠视网膜新生血管的抑制作用[J]. 中华眼底病杂志, 2020, 36(1): 53-59. DOI: 10.3760/cma.j.issn.1005-1015.2020.01.012.Huang LY, Ke YF, Lin TT, et al. Lentivirus-mediated polypyrimidine bundle binding protein-associated splicing factor inhibits retinal neovascularization in mice of oxygen-induced retinopathy[J]. Chin J Ocul Fundus Dis, 2020, 36(1): 53-59. DOI: 10.3760/cma.j.issn.1005-1015.2020.01.012.
13. 牛瑞, 东莉洁, 马腾, 等. 结缔组织生长因子重组干扰载体慢病毒颗粒的构建及其对视网膜血管内皮细胞内源性结缔组织生长因子表达的抑制作用[J]. 中华眼底病杂志, 2018, 34(6): 580-585. DOI: 10.3760/cma.j.issn.1005-1015.2018.06.011.Niu R, Dong LJ, Ma T, et al. Construction of connective tissue growth factor recombinant interference vector lentiviral particle and its inhibitory effect on endogenous connective tissue growth factor expression in retinal vascular endothelial cells[J]. Chin J Ocul Fundus Dis, 2018, 34(6): 580-585. DOI: 10.3760/cma.j.issn.1005-1015.2018.06.011.
14. Sun YY, Yang YF, Keller KE. Myosin-X silencing in the trabecular meshwork suggests a role for tunneling nanotubes in outflow regulation[J]. Invest Ophthalmol Vis Sci, 2019, 60(2): 843-851. DOI: 10.1167/iovs.18-26055.
15. Rivera VM, Gao GP, Grant RL, et al. Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer[J]. Blood, 2005, 105(4): 1424-1430. DOI: 10.1182/blood-2004-06-2501.
16. Lee SH, Kim YS, Nah SK, et al. Transduction patterns of adeno-associated viral vectors in a laser-induced choroidal neovascularization mouse model[J]. Mol Ther Methods Clin Dev, 2018, 9: 90-98. DOI: 10.1016/j.omtm.2018.01.008.
17. Brydon EM, Bronstein R, Buskin A, et al. AAV-mediated gene augmentation therapy restores critical functions in mutant PRPF31^+/- iPSC-derived RPE cells[J]. Mol Ther Methods Clin Dev, 2019, 15: 392-402. DOI: 10.1016/j.omtm.2019.10.014.
18. Quinn PM, Buck TM, Mulder AA, et al. Human iPSC-derived retinas recapitulate the fetal CRB1 CRB2 complex formation and demonstrate that photoreceptors and muller glia are targets of AAV5[J]. Stem Cell Reports, 2019, 12(5): 906-919. DOI: 10.1016/j.stemcr.2019.03.002.
19. Basche M, Kampik D, Kawasaki S, et al. Sustained and widespread gene delivery to the corneal epithelium via in situ transduction of limbal epithelial stem cells, using lentiviral and adeno-associated viral vectors[J]. Hum Gene Ther, 2018, 29(10): 1140-1152. DOI: 10.1089/hum.2018.115.
20. Manghwar H, Lindsey K, Zhang X, et al. CRISPR/Cas system: recent advances and future prospects for genome editing[J]. Trends Plant Sci, 2019, 24(12): 1102-1125. DOI: 10.1016/j.tplants.2019.09.006.
21. Lau CH, Suh Y. In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease[J]. F1000Res, 2017, 6: 2153. DOI: 10.12688/f1000research.11243.1.
22. Hung SS, Chrysostomou V, Li F, et al. AAV-mediated CRISPR/Cas gene editing of retinal cells in vivo[J]. Invest Ophthalmol Vis Sci, 2016, 57(7): 3470-3476. DOI: 10.1167/iovs.16-19316.
23. Yu W, Wu Z. Use of AAV vectors for CRISPR-mediated in vivo genome editing in the retina[J]. Methods Mol Biol, 2019, 1950: 123-139. DOI: 10.1007/978-1-4939-9139-6_7.
24. Cheng G, Tian K, Zhang L, et al. S100A4 gene silencing in oxygen-induced ischemic retinopathy inhibits retinal neovascularization via down-regulation of CREB expression[J]. Graefe’s Arch Clin Exp Ophthalmol, 2016, 254(1): 97-108. DOI: 10.1007/s00417-015-3158-0.
25. Li J, Wang JJ, Zhang SX. NADPH oxidase 4-derived H₂O₂ promotes aberrant retinal neovascularization via activation of VEGF receptor 2 pathway in oxygen-induced retinopathy[J/OL]. J Diabetes Res, 2015, 2015: 963289[2015-03-18]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381975/. DOI: 10.1155/2015/963289.
26. Han J, Li N. Adenoviral vector-mediated delivery of p21WAF1/CIP1 prevents retinal neovascularization in an oxygen-induced retinopathy model[J]. Curr Eye Res, 2016, 41(8): 1113-1117. DOI: 10.3109/02713683.2015.1090002.
27. Wang QM, Zhao XY, Zhi W, et al. IL-10 modified immature dendritic cells attenuate immune rejection in a rat model of high-risk corneal transplantation[J]. J Biomater Tiss Eng, 2017, 7(5): 408-412. DOI: 10.1166/jbt.2017.1578.
28. Kaufmann C, Mortimer LA, Brereton HM, et al. Interleukin-10 gene transfer in rat limbal transplantation[J]. Curr Eye Res, 2017, 42(11): 1426-1434. DOI: 10.1080/02713683.2017.1344714.
29. 李汉林, 谷晋, 周琼, 等. 腺病毒载体介导血管抑素防治兔高危角膜移植术后新生血管化的实验研究[J]. 江西医药, 2012, 47(2): 115-117. DOI: 10.3969/j.issn.1006-2238.2012.02.010.Li HL, Gu J, Zhou Q. Effects of recombinant adenovirus-mediated angiostatin on inhibiting high-risk keratoplasty neovascularization of rabbit[J]. Jiangxi Medical Journal, 2012, 47(2): 115-117. DOI: 10.3969/j.issn.1006-2238.2012.02.010.
30. Serratrice N, Cubizolle A, Ibanes S, et al. Corrective GUSB transfer to the canine mucopolysaccharidosis Ⅶ cornea using a helper-dependent canine adenovirus vector[J]. J Control Release, 2014, 181: 22-31. DOI: 10.1016/j.jconrel.2014.02.022.
31. Loewen N, Fautsch MP, Teo WL, et al. Long-term, targeted genetic modification of the aqueous humor outflow tract coupled with noninvasive imaging of gene expression in vivo[J]. Invest Ophthalmol Vis Sci, 2004, 45(9): 3091-3098. DOI: 10.1167/iovs.04-0366.
32. Aktas Z, Rao H, Slauson SR, et al. Proteasome inhibition increases the efficiency of lentiviral vector-mediated transduction of trabecular meshwork[J]. Invest Ophthalmol Vis Sci, 2018, 59(1): 298-310. DOI: 10.1167/iovs.17-22074.
33. Sun W, Li YN, Ye JF, et al. MEG3 is involved in the development of glaucoma through promoting the autophagy of retinal ganglion cells[J]. Eur Rev Med Pharmacol Sci, 2018, 22(9): 2534-2540. DOI: 10.26355/eurrev_201805_14942.
34. Song WT, Zhang XY, Xia XB. Atoh7 promotes the differentiation of muller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma[J]. Exp Biol Med (Maywood), 2015, 240(5): 682-690. DOI: 10.1177/1535370214560965.
35. He Y, Li HB, Li X, et al. MiR-124 promotes the growth of retinal ganglion cells derived from muller cells[J]. Cell Physiol Biochem, 2018, 45(3): 973-983. DOI: 10.1159/000487292.
36. Tan J, Liu G, Zhu X, et al. Lentiviral vector-mediated expression of exoenzyme C3 transferase lowers intraocular pressure in monkeys[J]. Mol Ther, 2019, 27(7): 1327-1338. DOI: 10.1016/j.ymthe.2019.04.021.
37. 田芳, 赵今稚, 黄亮瑜, 等. 高表达Krüppel样因子6对紫外线B诱导的人晶状体上皮细胞凋亡的影响[J]. 中华实验眼科杂志, 2019, 37(4): 257-262. DOI: 10.3760/cma.j.issn.2095-0160.2019.04.004.Tian F, Zhao JZ, Huang LY, et al. Effects of Krüppel-like factor 6 overexpression towards apoptosis of human lens epithelial cells with ultra violetradiation B treatment[J]. Chin J Exp Ophthalmol, 2019, 37(4): 257-262. DOI: 10.3760/cma.j.issn.2095-0160.2019.04.004.
38. 田芳, 赵今稚, 滕贺, 等. Krüppel样因子6经活化转录因子4通路对晶状体上皮细胞凋亡的调控作用[J]. 中华实验眼科杂志, 2018, 36(3): 181-186. DOI: 10.3760/cma.j.issn.2095-0160.2018.03.005.Tian F, Zhao JZ, Teng H, et al. Regulation of Krüppel-like factor 6 via activating transcription factor 4 pathway to apoptosis of human lens epithelial cells[J]. Chin J Exp Ophthalmol, 2018, 36(3): 181-186. DOI: 10.3760/cma.j.issn.2095-0160.2018.03.005.
39. 高美子, 黄亮瑜, 东莉洁, 等. Krüppel样因子6对于TGF-β1诱导的晶状体上皮细胞纤维化的调控作用研究[J]. 中国中医眼科杂志, 2018, 28(1): 4-11. DOI: 10.13444/j.cnki.zgzyykzz.2018.01.002.Gao MZ, Huang LY, Dong LJ, et al. Regulation of Krüppel-like Factor 6 on TGF-β1-induced fibrosis of lens epithelial cells[J]. Chinese Journal of Chinese Ophthalmology, 2018, 28(1): 4-11. DOI: 10.13444/j.cnki.zgzyykzz.2018.01.002.
40. 滕贺, 黄亮瑜, 田芳, 等. 衰老标记蛋白30高表达对紫外线诱导人晶状体上皮细胞凋亡的影响[J]. 中华眼科杂志, 2017, 53(11): 835-841. DOI: 10.3760/cma.j.issn.0412-4081.2017.11.007.Teng H, Huang LY, Tian F, et al. Effects of SMP-30 overexpression on apoptosis of human lens epithelial cells induced by ultraviolet B irradiation[J]. Chin J Ophthalmol, 2017, 53(11): 835-841. DOI: 10.3760/cma.j.issn.0412-4081.2017.11.007.
41. 刘勃实, 东莉洁, 李筱荣, 等. 慢病毒介导的微小RNA-191对小鼠视网膜新生血管的抑制作用[J]. 中华眼底病杂志, 2019, 35(5): 475-479. DOI: 10.3760/cma.j.issn.1005-1015.2019.05.010.Liu BS, Dong LJ, Li XR, et al. miR-191 inhibits oxygen-induced retinal neovascularization in mice[J]. Chin J Ocul Fundus Dis, 2019, 35(5): 475-479. DOI: 10.3760/cma.j.issn.1005-1015.2019.05.010.
42. Pang JJ, Chang B, Kumar A, et al. Gene therapy restores vision-dependent behavior as well as retinal structure and function in a mouse model of rpe65 leber congenital amaurosis[J]. Mol Ther, 2006, 13(3): 565-572. DOI: 10.1016/j.ymthe.2005.09.001.
43. Acland GM, Aguirre GD, Bennett J, et al. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness[J]. Mol Ther, 2005, 12(6): 1072-1082. DOI: 10.1016/j.ymthe.2005.08.008.
44. Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial[J]. Lancet, 2009, 374(9701): 1597-1605. DOI: 10.1016/s0140-6736(09)61836-5.
45. Bennett J, Wellman J, Marshall KA, et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial[J]. Lancet, 2016, 388(10045): 661-672. DOI: 10.1016/s0140-6736(16)30371-3.
46. Bennett J, Ashtari M, Wellman J, et al. AAV2 gene therapy readministration in three adults with congenital blindness[J/OL]. Sci Transl Med, 2012, 4(120): 120ra115[2012-02-01]. https://www.researchgate.net/publication/221822316_AAV2_Gene_Therapy_Readministration_in_Three_Adults_with_Congenital_Blindness. DOI: 10.1126/scitranslmed.3002865.
47. Maguire AM, Russell S, Wellman JA, et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials[J]. Ophthalmology, 2019, 126(9): 1273-1285. DOI: 10.1016/j.ophtha.2019.06.017.
48. Lai CM, Shen WY, Brankov M, et al. Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys[J]. Mol Ther, 2005, 12(4): 659-668. DOI: 10.1016/j.ymthe.2005.04.022.
49. Rakoczy EP, Magno AL, Lai CM, et al. Three-year follow-up of phase 1 and 2a rAAV. sFLT-1 subretinal gene therapy trials for exudative age-related macular degeneration[J]. Am J Ophthalmol, 2019, 204: 113-123. DOI: 10.1016/j.ajo.2019.03.006.
50. Heier JS, Kherani S, Desai S, et al. Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial[J]. Lancet, 2017, 390(10089): 50-61. DOI: 10.1016/s0140-6736(17)30979-0.
51. Taylor RL, Poulter JA, Downes SM, et al. Loss-of-function mutations in the CFH gene affecting alternatively encoded factor H-like 1 protein cause dominant early-onset macular drusen[J]. Ophthalmology, 2019, 126(10): 1410-1421. DOI: 10.1016/j.ophtha.2019.03.013.
52. Schnabolk G, Parsons N, Obert E, et al. Delivery of CR2-fH using aav vector therapy as treatment strategy in the mouse model of choroidal neovascularization[J]. Mol Ther Methods Clin Dev, 2018, 9: 1-11. DOI: 10.1016/j.omtm.2017.11.003.
53. Kwong JM, Gu L, Nassiri N, et al. AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury[J]. Gene Ther, 2015, 22(2): 138-145. DOI: 10.1038/gt.2014.105.
54. 刘爱华, 高美子, 黄亮瑜, 等. 叉头框转录因子F2小发夹RNA对人眼小梁网细胞外基质蛋白表达的抑制作用[J]. 中华实验眼科杂志, 2019, 37(6): 405-410. DOI: 10.3760/cma.j.issn.2095-0160.2019.06.002.Liu AH, Gao MZ, Huang LY, et al. The inhibitory effect of FoxF2 shRNA on the expression of extracellular matrix of human trabecular meshwork[J]. Chin J Exp Ophthalmol, 2019, 37(6): 405-410. DOI: 10.3760/cma.j.issn.2095-0160.2019.06.002.
55. Buie LK, Rasmussen CA, Porterfield EC, et al. Self-complementary AAV virus (scAAV) safe and long-term gene transfer in the trabecular meshwork of living rats and monkeys[J]. Invest Ophthalmol Vis Sci, 2010, 51(1): 236-248. DOI: 10.1167/iovs.09-3847.
56. Bogner B, Boye SL, Min SH, et al. Capsid mutated adeno-associated virus delivered to the anterior chamber results in efficient transduction of trabecular meshwork in mouse and rat[J/OL]. PLoS One, 2015, 10(6): 0128759[2015-06-08]. hhttps://core.ac.uk/display/89605988. DOI: 10.1371/journal.pone.0128759.
57. Wang L, Xiao R, Andres-Mateos E, et al. Single stranded adeno-associated virus achieves efficient gene transfer to anterior segment in the mouse eye[J/OL]. PLoS One. 2017, 12(8): 0182473[2017-08-01]. http://adsabs.harvard.edu/abs/2017PLoSO..1282473W. DOI: 10.1371/journal.pone.0182473.
58. O'Callaghan J, Crosbie DE, Cassidy PS, et al. Therapeutic potential of AAV-mediated MMP-3 secretion from corneal endothelium in treating glaucoma[J]. Hum Mol Genet, 2017, 26(7): 1230-1246. DOI: 10.1093/hmg/ddx028.
59. Fu X, Huu VAN, Duan Y, et al. Clinical applications of retinal gene therapies[J]. Pre Clin Med, 2018, 1(1): 5-20. DOI: 10.1093/pcmedi/pby004.
60. Zhu J, Ming C, Fu X, et al. Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors[J]. Cell Res, 2017, 27(6): 830-833. DOI: 10.1038/cr.2017.57.
61. Yu W, Mookherjee S, Chaitankar V, et al. Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice[J/OL]. Nat Commun, 2017, 8: 14716[2017-03-14]. https://www.nature.com/articles/ncomms14716. DOI: 10.1038/ncomms14716.
62. Suzuki K, Tsunekawa Y, Hernandez-Benitez R, et al. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration[J]. Nature, 2016, 540(7631): 144-149. DOI: 10.1038/nature20565.
63. McCullough KT, Boye SL, Fajardo D, et al. Somatic gene editing of GUCY2D by AAV-CRISPR/Cas9 alters retinal structure and function in mouse and macaque[J]. Hum Gene Ther, 2019, 30(5): 571-589. DOI: 10.1089/hum.2018.193.

Previous Article
Current status and progress of torpedo maculopathy
Next Article
Attach importance to individualized treatment of diabetic macular edema

Chinese Journal of Ocular Fundus Diseases

Application of virus-mediated gene transduction technology in ophthalmology research

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content