Genome Editing Abrogates Angiogenesis in Vivo
Open accessAbstract
Angiogenesis, in which vascular endothelial growth factor receptor (VEGFR) 2 plays an essential role, is associated with a variety of human diseases including proliferative diabetic retinopathy and wet age-related macular degeneration. Here we report that a system of adeno-associated virus (AAV)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) is used to deplete VEGFR2 in vascular endothelial cells (ECs), whereby the expression of SpCas9 is driven by an endothelial-specific promoter of intercellular adhesion molecule 2. We further show that recombinant AAV serotype 1 (rAAV1) transduces ECs of pathologic vessels, and that editing of genomic VEGFR2 locus using rAAV1-mediated CRISPR/Cas9 abrogates angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization. This work establishes a strong foundation for genome editing as a strategy to treat angiogenesis-associated diseases.
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Recent efforts to address the problem of frequent intravitreal injections have employed gene editing strategies like targeting VEGFA using CRISPR-Cas9.
“Recent efforts to address this problem have employed gene editing strategies like targeting VEGFA using CRISPR-Cas9 (43, 45).”
From Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina (2024) · cites this paper as [45]
The Introduction and Discussion describe AAV-mediated CRISPR-Cas9 editing as a potential alternative to anti-VEGF treatment that requires chronic administration. But this study edits genomic VEGFR2, not VEGFA; the claimed target is incorrect. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA study delivering Cas9 and gRNA targeting VEGFR2 in AAV1 by intravitreal injection to WT C57BL/6J mice reported no damage to the retina four weeks post-injection.
“A study aimed to use genome editing to treat angiogenesis-associated diseases by packaging Cas9 and gRNA targeting vascular endothelial growth factor receptor 2 (VEGFR2) in AAV1 and delivering it by intravitreal injections to the eye of WT C57BL/6J mice.They analyzed toxicity and inflammation by imaging the fundus as well as immunolabeling the retina for inflammation markers but reported no damage”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [36]
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A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116 · see citing works
Angiogenesis in cancer, vascular, rheumatoid and other disease
Folkman, J. (1995) · Nature Medicine · doi:10.1038/nm0195-27 · Cited by 7,627 · see citing works
Cillà, S. D., Farruggio, S., Vujosevic, S., Raina, G., Filippini, D. A., Gatti, V., Clemente, N., Mary, D., Vezzola, D., Casini, G., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479441 · Cited by 5,154 · see citing works
Tumor Cells Secrete a Vascular Permeability Factor That Promotes Accumulation of Ascites Fluid
Senger, D. R., Galli, S. J., Dvořàk, A. M., Perruzzi, C. A., Harvey, V. S., & Dvorak, H. F. (1983) · Science · doi:10.1126/science.6823562 · Cited by 3,969 · see citing works
Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Bergers, G., Brekken, R., McMahon, G., Vu, T. H., Itoh, T., Tamaki, K., Tanzawa, K., Thorpe, P., Itohara, S., Werb, Z., et al. (2000) · Nature Cell Biology · doi:10.1038/35036374 · Cited by 2,797 · see citing works
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145 · see citing works
Effect of gene therapy on visual function in Leber’s congenital amaurosis
Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802268 · Cited by 1,924 · see citing works
Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity
Mintz-Hittner, H. A., Kennedy, K. A., & Chuang, A. Z. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1007374 · Cited by 1,451 · see citing works
Therapeutic genome editing: prospects and challenges
Cox, D. B. T., Platt, R. J., & Zhang, F. (2015) · Nature Medicine · doi:10.1038/nm.3793 · Cited by 1,336 · see citing works
Self-citationTherapeutic Potential of Ex Vivo Expanded Endothelial Progenitor Cells for Myocardial Ischemia
Kawamoto, A., Gwon, H.-C., Iwaguro, H., Yamaguchi, J.-I., Uchida, S., Masuda, H., Silver, M., Ma, H., Kearney, M., Isner, J. M., et al. (2001) · Circulation · doi:10.1161/01.cir.103.5.634 · Cited by 1,219 · see citing works
In vivo gene editing in dystrophic mouse muscle and muscle stem cells
Tabebordbar, M., Zhu, K., Cheng, J. K. W., Chew, W. L., Widrick, J. J., Yan, W. X., Maesner, C., Wu, E. Y., Xiao, R., Ran, F. A., et al. (2016) · Science · doi:10.1126/science.aad5177 · Cited by 1,046 · see citing works
Self-citationHolmes, K., Roberts, O. L., Thomas, A. M., & Cross, M. J. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.05.013 · Cited by 1,020 · see citing works
Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., et al. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.107 · Cited by 954 · see citing works
In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9
Swiech, L., Heidenreich, M., Banerjee, A., Habib, N., Li, Y., Trombetta, J., Sur, M., & Zhang, F. (2015) · Nature Biotechnology · doi:10.1038/nbt.3055 · Cited by 772 · see citing works
Self-citationJessup, M., Greenberg, B., Mancini, D., Cappola, T., Pauly, D. F., Jaski, B., Yaroshinsky, A., Zsebo, K. M., Dittrich, H., & Hajjar, R. J. (2011) · Circulation · doi:10.1161/circulationaha.111.022889 · Cited by 760 · see citing works
Chakravarthy, U., Harding, S. P., Rogers, C. A., Downes, S. M., Lotery, A. J., Culliford, L. A., & Reeves, B. C. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61501-9 · Cited by 748 · see citing works
Connor, K. M., Krah, N. M., Dennison, R. J., Aderman, C. M., Chen, J., Guerin, K. I., Sapieha, P. S., Stahl, A., Willett, K. L., & Smith, L. E. H. (2009) · Nature Protocols · doi:10.1038/nprot.2009.187 · Cited by 742 · see citing works
Giraudo, E., Inoue, M., & Hanahan, D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422087 · Cited by 700 · see citing works
The Mouse Retina as an Angiogenesis Model
Stahl, A., Connor, K. M., Sapieha, P. S., Chen, J., Dennison, R. J., Krah, N. M., Seaward, M. R., Willett, K. L., Aderman, C. M., Guerin, K. I., et al. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5176 · Cited by 610 · see citing works
Production and characterization of adeno-associated viral vectors
Grieger, J. C., Choi, V. W., & Samulski, R. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.207 · Cited by 567 · see citing works
An essential receptor for adeno-associated virus infection
Pillay, S., Meyer, N. L., Puschnik, A. S., Davulcu, O., Diep, J., Ishikawa, Y., Jae, L. T., Wosen, J. E., Nagamine, C. M., Chapman, M. S., et al. (2016) · Nature · doi:10.1038/nature16465 · Cited by 532 · see citing works
Epidemiology of diabetic retinopathy and macular oedema: A systematic review
Williams, R., Airey, M., Baxter, H., Forrester, J., Kennedy-Martin, T., & Girach, A. (2004) · Eye · doi:10.1038/sj.eye.6701476 · Cited by 472 · see citing works
Muller, Y. A., Li, B., Christinger, H. W., Wells, J. A., Cunningham, B. C., & de Vos, A. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7192 · Cited by 452 · see citing works
Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice
Lambert, V., Lecomte, J., Hansen, S., Blacher, S., Gonzalez, M.-L. A., Struman, I., Sounni, N. E., Rozet, E., Tullio, P. D., Foidart, J. M., et al. (2013) · Nature Protocols · doi:10.1038/nprot.2013.135 · Cited by 420 · see citing works
Gaudet, D., Méthot, J., Déry, S., Brisson, D., Essiembre, C., Tremblay, G., Tremblay, K., de Wal, J., Twisk, J., van den Bulk, N., et al. (2013) · Gene Therapy · doi:10.1038/gt.2012.43 · Cited by 404 · see citing works
Shima, D. T., Adamis, A. P., Ferrara, N., Yeo, K.-T., Yeo, T.-K., Allende, R., Folkman, J., & D'Amore, P. A. (1995) · Molecular Medicine · doi:10.1007/bf03401566 · Cited by 352 · see citing works
Self-citationEllis, B. L., Hirsch, M. L., Barker, J. C., Connelly, J. P., Steininger, R. J., & Porteus, M. H. (2013) · Virology Journal · doi:10.1186/1743-422x-10-74 · Cited by 252 · see citing works
Axl is essential for VEGF‐A‐dependent activation of PI3K/Akt
Ruan, G.-X., & Kazlauskas, A. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.21 · Cited by 224 · see citing works
Adeno-associated virus vector integration.
Deyle, D. R., & Russell, D. W. (2009) · PubMed · Cited by 206 · see citing works
Gene therapy for lipoprotein lipase deficiency
Gaudet, D., Méthot, J., & Kastelein, J. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283555a7e · Cited by 178 · see citing works
Giani, A., Thanos, A., Roh, M., Connolly, E. J., Trichonas, G., Kim, I. K., Gragoudas, E. S., Vavvas, D. G., & Miller, J. W. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6266 · Cited by 97 · see citing works
Suzuki, M., Nagai, N., Izumi‐Nagai, K., Shinoda, H., Koto, T., Uchida, A., Mochimaru, H., Yuki, K., Sasaki, M., Tsubota, K., et al. (2014) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2013-304670 · Cited by 97 · see citing works
PGC-1α Regulates Normal and Pathological Angiogenesis in the Retina
Saint‐Geniez, M., Jiang, A., Abend, S., Liu, L., Sweigard, H., Connor, K. M., & Arany, Z. P. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.09.003 · Cited by 70 · see citing works
Lei, H., Romeo, G. R., & Kazlauskas, A. (2004) · Circulation Research · doi:10.1161/01.res.0000124979.46214.e3 · Cited by 65 · see citing works
Self-citationEditing VEGFR2 Blocks VEGF-Induced Activation of Akt and Tube Formation
Huang, X., Zhou, G., Wu, W., Ma, G., D'Amore, P. A., Mukai, S., & Lei, H. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-20537 · Cited by 61 · see citing works
Self-citationChitranshi, N., Gupta, V., Kumar, S., & Graham, S. L. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160921087 · Cited by 49 · see citing works
Update on treatments for diabetic macular edema
Fraser‐Bell, S., Kaines, A., & Hykin, P. (2008) · Current Opinion in Ophthalmology · doi:10.1097/icu.0b013e3282fb7c45 · Cited by 49 · see citing works
CRISPR/Cas9: Prospects and Challenges
Zhang, F. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.29002.fzh · Cited by 42 · see citing works
Self-citationDuan, Y., Ma, G., Huang, X., D'Amore, P. A., Zhang, F., & Lei, H. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.729467 · Cited by 31 · see citing works
Self-citationLei, H., Qian, C. X., Lei, J., Haddock, L. J., Mukai, S., & Kazlauskas, A. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.01248-14 · Cited by 27 · see citing works
Self-citationIdentification of Synthetic Endothelial Cell-Specific Promoters by Use of a High-Throughput Screen
Dai, C., McAninch, R., & Sutton, R. (2004) · Journal of Virology · doi:10.1128/jvi.78.12.6209-6221.2004 · Cited by 17 · see citing works
Jiang, A., Abend, S., D'Amore, P. A., Saint‐Geniez, M., & Arany, Z. P. (2011) · Investigative Ophthalmology & Visual Science · Cited by 3 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.110 · Cited by 306 · see citing works
Delivery of CRISPR-Cas tools for in vivo genome editing therapy: Trends and challenges
Taha, E. A., Lee, J., & Hotta, A. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.01.013 · Cited by 259 · see citing works
Erratum: Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.158 · Cited by 248 · see citing works
Delivery of CRISPR/Cas systems for cancer gene therapy and immunotherapy
Song, X., Liu, C., Wang, N., Huang, H., He, S., Gong, C., & Wei, Y. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.04.010 · Cited by 214 · see citing works
Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies
Whitehead, M. A., Wickremasinghe, S., Osborne, A., van Wijngaarden, P., & Martin, K. R. G. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1545836 · Cited by 198 · see citing works
Vimalraj, S. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.09.129 · Cited by 192 · see citing works
Lau, C.-H., & Suh, Y. (2017) · F1000Research · doi:10.12688/f1000research.11243.1 · Cited by 161 · see citing works
Xue, L., Hamilton, A. G., Zhao, G., Xiao, Z., El-Mayta, R. D., Han, X., Gong, N., Xiong, X., Xu, J., Figueroa‐Espada, C. G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45422-9 · Cited by 144 · see citing works
A Self-Deleting AAV-CRISPR System for In Vivo Genome Editing
Li, A., Lee, C. M., Hurley, A. E., Jarrett, K. E., Giorgi, M. D., Lu, W., Balderrama, K. S., Doerfler, A. M., Deshmukh, H., Ray, A., et al. (2018) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2018.11.009 · Cited by 129 · see citing works
Xue, L., Zhao, G., Gong, N., Han, X., Shepherd, S. J., Xiong, X., Xiao, Z., Palanki, R., Xu, J., Swingle, K. L., et al. (2024) · Nature Nanotechnology · doi:10.1038/s41565-024-01747-6 · Cited by 123 · see citing works
Wan, T. Y., Niu, D., Wu, C., Xu, F., Church, G. M., & Yuan, P. (2019) · Materials Today · doi:10.1016/j.mattod.2018.12.003 · Cited by 118 · see citing works
Sharpening the Molecular Scissors: Advances in Gene-Editing Technology
Broeders, M., Herrero-Hernandez, P., Ernst, M. P. T., van der Ploeg, A. T., & Pijnappel, W. W. M. P. (2019) · iScience · doi:10.1016/j.isci.2019.100789 · Cited by 110 · see citing works
Sun, S., Qin, W., Tang, X., Meng, Y., Hu, W., Zhang, S., Qian, M., Liu, Z., Cao, X., Pang, Q., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay5556 · Cited by 107 · see citing works
Gene therapy for visual loss: Opportunities and concerns
Lee, J. H., Wang, J.-H., Chen, J., Li, F., Edwards, T. L., Hewitt, A. W., & Liu, G. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.08.003 · Cited by 101 · see citing works
Koo, T., Park, S. W., Jo, D. H., Kim, D., Kim, J. H., Cho, H.-Y., Kim, J. H., Kim, J. H., & Kim, J. (2018) · Nature Communications · doi:10.1038/s41467-018-04175-y · Cited by 95 · see citing works
Genome editing methods in animal models
Lee, H., Yoon, D. E., & Kim, K. (2020) · Animal Cells and Systems · doi:10.1080/19768354.2020.1726462 · Cited by 81 · see citing works
Gene Therapy Intervention in Neovascular Eye Disease: A Recent Update
Lin, F.-L., Wang, P.-Y., Chuang, Y.-F., Wang, J.-H., Wong, V. H. Y., Bui, B. V., & Liu, G.-S. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.06.029 · Cited by 74 · see citing works
Periosteal Tissue Engineering: Current Developments and Perspectives
Lou, Y., Wang, H., Ye, G., Li, Y., Liu, C., Yu, M., & Ying, B. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202100215 · Cited by 74 · see citing works
CRISPR-Cas9 genome engineering: Treating inherited retinal degeneration
Burnight, E. R., Giacalone, J. C., Cooke, J. A., Thompson, J. R., Bohrer, L. R., Chirco, K. R., Drack, A. V., Fingert, J. H., Worthington, K. S., Wiley, L. A., et al. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.03.003 · Cited by 75 · see citing works
Chen, D.-Y., Sun, N.-H., Chen, X. '., Gong, J.-J., Yuan, S.-T., Hu, Z.-Z., Lu, N., Körbelin, J., Fukunaga, K., Liu, Q., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci135296 · Cited by 72 · see citing works
Xin, T., Zhang, Y., Pu, X., Gao, R., Xu, Z., & Song, J. (2018) · Science China Life Sciences · doi:10.1007/s11427-018-9352-7 · Cited by 66 · see citing works
Self-citationUpdates on Gene Therapy for Diabetic Retinopathy
Wang, J.-H., Roberts, G. E., & Liu, G. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01308-w · Cited by 62 · see citing works
Delivery Approaches for Therapeutic Genome Editing and Challenges
Ates, I., Rathbone, T., Stuart, C., Bridges, P. H., & Cottle, R. N. (2020) · Genes · doi:10.3390/genes11101113 · Cited by 60 · see citing works
Host immune responses after suprachoroidal delivery of AAV8 in nonhuman primate eyes
Chung, S. H., Mollhoff, I. N., Mishra, A., Sin, T.-N., Ngo, T., Ciulla, T., Sieving, P., Thomasy, S. M., & Yiu, G. (2021) · Human Gene Therapy · doi:10.1089/hum.2020.281 · Cited by 57 · see citing works
Jo, D. H., Koo, T., Cho, C. S., Kim, J. H., Kim, J.-S., & Kim, J. H. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2018.10.009 · Cited by 57 · see citing works
Ren, D., Fisson, S., Dalkara, D., & Ail, D. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14091973 · Cited by 52 · see citing works
Interleukin-17: The Role for Pathological Angiogenesis in Ocular Neovascular Diseases
Li, Y., & Zhou, Y. (2019) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.247.87 · Cited by 51 · see citing works
CRISPR–Cas9 in genome editing: Its function and medical applications
Khadempar, S., Familghadakchi, S., Motlagh, R. A., Farahani, N., Dashtiahangar, M., Rezaei, H., & Hayat, S. M. G. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27476 · Cited by 51 · see citing works
Strategies for the CRISPR-Based Therapeutics
Li, B., Niu, Y., Ji, W., & Dong, Y. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.11.006 · Cited by 49 · see citing works
TAK1 signaling is a potential therapeutic target for pathological angiogenesis
Zhu, L., Lama, S., Tu, L., Dusting, G. J., Wang, J.-H., & Liu, G. (2021) · Angiogenesis · doi:10.1007/s10456-021-09787-5 · Cited by 48 · see citing works
Chakravarthy, H., & Devanathan, V. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1188-x · Cited by 46 · see citing works
AAV-CRISPR/Cas9–Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro
Wu, W., Duan, Y., Ma, G., Zhou, G., Park‐Windhol, C., D'Amore, P. A., & Lei, H. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-21902 · Cited by 43 · see citing works
Self-citationCastro, B. F. M., Steel, J. C., & Layton, C. J. (2023) · BioDrugs · doi:10.1007/s40259-023-00629-y · Cited by 39 · see citing works
CRISPR-based VEGF suppression using paired guide RNAs for treatment of choroidal neovascularization
Chung, S. H., Sin, T.-N., Dang, B., Ngo, T., Lo, T., Lent-Schochet, D., Meleppat, R. K., Zawadzki, R. J., & Yiu, G. (2022) · Molecular Therapy - Nucleic Acids · doi:10.1016/j.omtn.2022.04.015 · Cited by 37 · see citing works
pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy
Guo, S., Li, C., Wang, C., Cao, X., Liu, X., Liang, X.-J., Huang, Y., & Weng, Y. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.09.001 · Cited by 36 · see citing works
CRISPR/Cas-Dependent and Nuclease-Free In Vivo Therapeutic Gene Editing
Dasgupta, I., Flotte, T. R., & Keeler, A. M. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.013 · Cited by 37 · see citing works
The application and progression of CRISPR/Cas9 technology in ophthalmological diseases
Hu, X., Zhang, B., Li, X., Li, M., Wang, Y., Dan, H., Zhou, J., Wei, Y., Ge, K., Li, P., et al. (2022) · Eye · doi:10.1038/s41433-022-02169-1 · Cited by 35 · see citing works
Chung, S. H., Mollhoff, I. N., Nguyen, U. T. T., Nguyen, A. B., Stucka, N., Tieu, E., Manna, S. K., Meleppat, R. K., Zhang, P., Nguyen, E. L., et al. (2020) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2020.01.006 · Cited by 35 · see citing works
Comparison of CRISPR/Cas Endonucleases for in vivo Retinal Gene Editing
Li, F., Wing, K., Wang, J.-H., Luu, C. D., Bender, J. A., Chen, J., Wang, Q., Lu, Q., Nguyen Tran, M. T., Young, K. M., et al. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.570917 · Cited by 34 · see citing works
PI3Kδ as a Novel Therapeutic Target in Pathological Angiogenesis
Wu, W., Zhou, G., Han, H., Huang, X., Jiang, H., Mukai, S., Kazlauskas, A., Cui, J. Z., Matsubara, J. A., Vanhaesebroeck, B., et al. (2020) · Diabetes · doi:10.2337/db19-0713 · Cited by 33 · see citing works
Self-citationIn Vivo Applications of CRISPR-Based Genome Editing in the Retina
Yu, W., & Wu, Z. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00053 · Cited by 31 · see citing works
Ocular RNA nanomedicine: engineered delivery nanoplatforms in treating eye diseases
Zhang, Y., Shi, Y., Khan, M. M., Xiao, F., Chen, W., Tao, W., Yao, K., & Kong, N. (2024) · Trends in biotechnology · doi:10.1016/j.tibtech.2024.05.002 · Cited by 30 · see citing works
Sabra, M., Karbasiafshar, C., Aboulgheit, A., Raj, S., Abid, M. R., & Sellke, F. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073722 · Cited by 30 · see citing works
Liu, X., Huang, K., Zhang, F., Huang, G., Wang, L., Wu, G., Ren, H., Yang, G., & Lin, Z. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02614-1 · Cited by 30 · see citing works
Self-citationTyumentseva, M. A., Tyumentsev, A. I., & Акимкин, В. Г. (2021) · PLoS ONE · doi:10.1371/journal.pone.0259812 · Cited by 29 · see citing works
Gene editing prospects for treating inherited retinal diseases
Benati, D., Patrizi, C., & Recchia, A. (2019) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2019-106473 · Cited by 28 · see citing works
Peeling back the layers of immunogenicity in Cas9-based genomic medicine
Stigzelius, V., Cavallo, A. L., Chandode, R. K., & Nitsch, R. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.06.045 · Cited by 29 · see citing works
Nanotechnology for Age-Related Macular Degeneration
Yang, B. X., Li, G., Liu, J., Li, X., Zhang, S., Sun, F., & Liu, W. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13122035 · Cited by 29 · see citing works
Progress in the application of CRISPR: From gene to base editing
Wu, W., Yang, Y., & Lei, H. (2018) · Medicinal Research Reviews · doi:10.1002/med.21537 · Cited by 27 · see citing works
Self-citationGene-based therapeutics for acquired retinal disease: opportunities and progress
Tan, T.-E., Fenner, B. J., Barathi, V. A., Tun, S. B. B., Wey, Y. S., Tsai, A. S. H., Su, X., Lee, S. Y., Cheung, C. M. G., Wong, T. Y., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.795010 · Cited by 26 · see citing works
Targeting vascular endothelial growth factor using retinal gene therapy
Chung, S. H., Frick, S. L., & Yiu, G. C. (2021) · Annals of Translational Medicine · doi:10.21037/atm-20-4417 · Cited by 25 · see citing works
Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications
Zhou, L., & Yao, S. (2023) · Molecular Biomedicine · doi:10.1186/s43556-023-00115-5 · Cited by 27 · see citing works
Viral-vector-delivered anti-angiogenic therapies to the eye
Koponen, S., Kokki, E., Kinnunen, K., & Ylä-Herttuala, S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13020219 · Cited by 24 · see citing works
CRISPR-Based Genome Editing as a New Therapeutic Tool in Retinal Diseases
Rasoulinejad, S. A., & Maroufi, F. (2021) · Molecular Biotechnology · doi:10.1007/s12033-021-00345-4 · Cited by 24 · see citing works
Fuentes, C., & Schaffer, D. V. (2018) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2018.08.003 · Cited by 23 · see citing works
Angiogenic lncRNAs: A potential therapeutic target for ischaemic heart disease
Xu, Z.-M., Huang, F., & Huang, W.-Q. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.09.022 · Cited by 22 · see citing works
Gene Therapy in Diabetic Retinopathy and Diabetic Macular Edema: An Update
Odio-Herrera, M., Loaiza, G. O., & Wu, L. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14093205 · Cited by 24 · see citing works
Genome Editing with AAV-BR1-CRISPR in Postnatal Mouse Brain Endothelial Cells
Song, X., Cui, Y., Wang, Y., Zhang, Y., He, Q., Yu, Z., Xu, C., Ning, H., Han, Y., Cai, Y., et al. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.64188 · Cited by 20 · see citing works
Zhang, M., Lu, X., Luo, L., Dou, J., Zhang, J., Li, G., Li, Z., & Sun, F. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02943-1 · Cited by 20 · see citing works
CRISPR Technology for Ocular Angiogenesis
Chung, S. H., Sin, T.-N., Ngo, T., & Yiu, G. C. (2020) · Frontiers in Genome Editing · doi:10.3389/fgeed.2020.594984 · Cited by 21 · see citing works
Use of AAV Vectors for CRISPR-Mediated In Vivo Genome Editing in the Retina
Yu, W., & Wu, Z. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9139-6_7 · Cited by 20 · see citing works
Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina
Kumar, S., Hsiao, Y.-W., Wong, V. H. Y., Aubin, D., Wang, J.-H., Lisowski, L., Rakoczy, E. P., Li, F., Alarcon-Martinez, L., Gonzalez-Cordero, A., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2408345121 · Cited by 19 · see citing works
CRISPR Systems Suitable for Single AAV Vector Delivery
Stevanovic, M., Piotter, E., McClements, M. E., & MacLaren, R. E. (2021) · Current Gene Therapy · doi:10.2174/1566523221666211006120355 · Cited by 19 · see citing works
Toward the Treatment of Inherited Diseases of the Retina Using CRISPR-Based Gene Editing
Hernández-Juárez, J., Rodríguez‐Uribe, G., & Borooah, S. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.698521 · Cited by 19 · see citing works
Yang, Y., Huang, X., Ma, G., Cui, J. Z., Matsubara, J. A., Kazlauskas, A., Zhao, J., Wang, J., & Lei, H. (2020) · Experimental Eye Research · doi:10.1016/j.exer.2020.108116 · Cited by 18 · see citing works
Self-citationBiallelic CCM3 mutations cause a clonogenic survival advantage and endothelial cell stiffening
Schwefel, K., Spiegler, S., Ameling, S., Much, C. D., Pilz, R. A., Otto, O., Völker, U., Felbor, U., & Rath, M. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14075 · Cited by 18 · see citing works
Improvement of muscular atrophy by AAV–SaCas9-mediated myostatin gene editing in aged mice
Weng, S., Gao, F., Wang, J., Li, X., Chu, B., Yang, G., & Yang, G. (2020) · Cancer Gene Therapy · doi:10.1038/s41417-020-0178-7 · Cited by 17 · see citing works
Han, H., Yang, Y., Wu, Z., Liu, B., Dong, L., Deng, H., Tian, J., & Lei, H. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110999 · Cited by 17 · see citing works
Self-citationCRISPR-dcas9 Optogenetic Nanosystem for the Blue Light-Mediated Treatment of Neovascular Lesions
Li, J., Hao, Y., Pan, H., Zhang, Y., Cheng, G., Liu, B., Chang, J. K., & Wang, H. (2021) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c01465 · Cited by 17 · see citing works
Experiment-Based Interventions to Diabetic Retinopathy: Present and Advances
Liu, S., Ju, Y., & Gu, P. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137005 · Cited by 16 · see citing works
Unconventional avenues to decelerate diabetic retinopathy
Takkar, B., Sheemar, A., Jayasudha, R., Soni, D., Narayanan, R., Venkatesh, P., Shivaji, S., & Das, T. (2022) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2022.06.004 · Cited by 16 · see citing works
Chuang, K., Ma, F., & Priore, L. V. D. (2017) · PubMed Central · Cited by 15 · see citing works
CRISPR/Cas9 genome surgery for retinal diseases
Xu, C. L., Park, K. S., & Tsang, S. H. (2018) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2018.05.001 · Cited by 15 · see citing works
Mutation-independent therapies for retinal diseases: focus on gene-based approaches
Carrella, S., Indrieri, A., Franco, B., & Banfi, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.588234 · Cited by 14 · see citing works
AAV-mediated in vivo genome editing in vascular endothelial cells
Wu, W., Yang, Y., Yao, F., Dong, L., Xia, X., Zhang, S., & Lei, H. (2020) · Methods · doi:10.1016/j.ymeth.2020.12.001 · Cited by 14 · see citing works
Self-citationChen, N., Hu, Z., Yang, Y., Han, H., & Lei, H. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2019.107716 · Cited by 14 · see citing works
Self-citationEnhancing Understanding of the Visual Cycle by Applying CRISPR/Cas9 Gene Editing in Zebrafish
Ward, R. H. R., Sundaramurthi, H., Giacomo, V. D., & Kennedy, B. N. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00037 · Cited by 13 · see citing works
CRISPR/Cas systems usher in a new era of disease treatment and diagnosis
Li, R., Wang, Q., She, K., Lu, F., & Yang, Y. (2022) · Molecular Biomedicine · doi:10.1186/s43556-022-00095-y · Cited by 12 · see citing works
Idelalisib inhibits experimental proliferative vitroretinopathy
Dong, L., Han, H., Huang, X., Ma, G., Dong, F., Qi, H., Han, Z., Wang, L., Tian, J., Vanhaesebroeck, B., et al. (2022) · Laboratory Investigation · doi:10.1038/s41374-022-00822-7 · Cited by 12 · see citing works
Self-citationGenome Editing in Retinal Diseases using CRISPR Technology
Yiu, G. C. (2017) · Ophthalmology Retina · doi:10.1016/j.oret.2017.09.015 · Cited by 12 · see citing works
Roles and mechanisms of long non-coding RNAs in age-related macular degeneration
Zhang, R., Wang, L., Yang, L., Gui, C., Pei, Y., & Zhou, G. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e22307 · Cited by 11 · see citing works
Self-citationLi, H., & Huang, X. (2025) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2025.12893 · Cited by 11 · see citing works
Self-citationWu, Y., Lin, X., Hong, H., Fung, Y. L., Cao, X., Tse, J. K. Y., Li, T. H., Chan, T., & Tian, X. Y. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113172 · Cited by 10 · see citing works
Normal vitreous promotes angiogenesis via activation of Axl
Wu, W., Xia, X., Tang, L., Yao, F., Xu, H., & Lei, H. (2020) · The FASEB Journal · doi:10.1096/fj.201903105r · Cited by 10 · see citing works
Self-citationPuranen, J., Koponen, S., Nieminen, T., Kanerva, I., Kokki, E., Toivanen, P., Urtti, A., Ylä-Herttuala, S., & Ruponen, M. (2022) · Experimental Eye Research · doi:10.1016/j.exer.2022.109237 · Cited by 9 · see citing works
Basic and Clinical Application of Adeno-Associated Virus–Mediated Genome Editing
He, X., Xie, H., Liu, X., & Gu, F. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.190 · Cited by 7 · see citing works
Toutounchian, S., Ahmadbeigi, N., & Mansouri, V. (2022) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2022.0022 · Cited by 9 · see citing works
In vivo editing of the pan-endothelium by immunity evading simian adenoviral vector
Lőrincz, R., Alvarez, A. B., Walkey, C. J., Mendonça, S. A., Lu, Z. H., Martinez, A. E., Ljungberg, M. C., Heaney, J. D., Lagor, W. R., & Curiel, D. T. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114189 · Cited by 9 · see citing works
Nucleic Acid Delivery to the Vascular Endothelium
Reschke, M., Piotrowski-Daspit, A. S., Pober, J. S., & Saltzman, W. M. (2022) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c00653 · Cited by 9 · see citing works
Toward In Vivo Gene Therapy Using CRISPR
Skipper, K. A., & Mikkelsen, J. G. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9170-9_18 · Cited by 8 · see citing works
Exploitation of enhanced prime editing for blocking aberrant angiogenesis
Huang, X., Wu, W., Qi, H., Yan, X., Dong, L., Yang, Y., Zhang, Q., Ma, G., Zhang, G., & Lei, H. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.07.006 · Cited by 8 · see citing works
Self-citationHao, Y., Du, T., Pang, G., Li, J., Pan, H., Zhang, Y., Wang, L., Chang, J. K., Zhou, E., & Wang, H. (2020) · Nano Research · doi:10.1007/s12274-020-2998-z · Cited by 8 · see citing works
Long Non-Coding RNA PNKY Modulates the Development of Choroidal Neovascularization
Shi, L., Han, X., Liu, C., Li, X., Lu, S., Jiang, Q. L., & Yao, J. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.836031 · Cited by 8 · see citing works
A Novel Role of IL13Rα2 in the Pathogenesis of Proliferative Vitreoretinopathy
Qi, H., Dong, L., Dong, F., Chen, L., Wang, Y., Fan, N., Mao, X., Wu, W., Yan, X., Zhang, G., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.831436 · Cited by 7 · see citing works
Self-citationCancer metastases: Tailoring the targets
Pote, M. S., Singh, D., A, A. M., Suchita, J., & Gacche, R. N. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e35369 · Cited by 7 · see citing works
Genome Editing of Pik3cd Impedes Abnormal Retinal Angiogenesis
Wu, W., Ma, G., Qi, H., Dong, L., Chen, F., Wang, Y., Mao, X., Guo, X., Cui, J. Z., Matsubara, J. A., et al. (2022) · Human Gene Therapy · doi:10.1089/hum.2022.079 · Cited by 7 · see citing works
Self-citationZeng, L., Wei, Y., Qiu, Y., Bi, R., Peng, H., Hu, B., & Li, Y. (2025) · International Journal of Nanomedicine · doi:10.2147/ijn.s521960 · Cited by 7 · see citing works
Monteiro, C. J., Heery, D. M., & Whitchurch, J. B. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-33325-5_2 · Cited by 6 · see citing works
Hu, S., Chen, Y., Xie, D., Xu, K., Fu, Y., Chi, W., Liu, H., & Huang, J. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1383 · Cited by 7 · see citing works
Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls
Berkowitz, S. T., & Finn, A. P. (2024) · Current Opinion in Ophthalmology · doi:10.1097/icu.0000000000001043 · Cited by 7 · see citing works
- Authors
- Huang, X., Zhou, G., Wu, W., Duan, Y., Ma, G., Song, J., Xiao, R., Vandenberghe, L., Zhang, F., D’Amore, P. A., & Lei, H.
- Affiliations
- Massachusetts Eye and Ear Infirmary (US)
- Broad Institute (US)
- Corresponding author
- Lei, Hetian
- ORCID
- Venue
- Nature Communications
- Published
- 2017-07-24
- Volume
- 8
- Issue
- 1
- Pages
- 112-112
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5524639
- OpenAlex
- W2735017428
- Cited by
- 142
- References
- 42
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 14 · 2023: 17 · 2022: 20 · 2021: 19 · 2020: 19 · 2019: 8 · 2018: 21 · 2017: 4
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Nature
- Funders
- National Institutes of Health
- National Eye Institute (R01EY012509, P30EY003790)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- angiogenesis, VEGFR2, CRISPR/Cas9 genome editing, vascular endothelial cells, oxygen-induced retinopathy, diabetic retinopathy, age-related macular degeneration, gene silencing
- MeSH terms
- Gene Editing, Dependovirus, Animals, Cells, Cultured, Female, Humans, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Neovascularization, Pathologic, Blotting, Western, Retinal Neovascularization, Choroidal Neovascularization, Vascular Endothelial Growth Factor Receptor-2, Endothelial Cells, CRISPR-Cas Systems
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