- 1. Department of Ophthalmology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing 101199, China;
- 2. Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing 100005, China;
Jin Zibing,
Email: jinzibing@foxmail.com
At present, the treatment of hereditary retinopathy depends on gene replacement or editing therapy, and adeno-associated virus (AAV) vector is one of the most widely used gene transfer vectors. There are currently three ways to deliver AAV vector-mediated target genes to the retina. Intravitreal injection of AAV vector is currently the most commonly used delivery route, which can effectively improve the functions of retina disorders such as blinding retinal dystrophy in mice. Moreover, studies on X-linked retinoschisis have been undergoing clinical trials, but intravitreal injection has poor transduction in retinal pigment epithelium (RPE) cell layer and photoreceptor cell (PR) layer. Subretinal injection of AAV vector can deliver the target gene to the local retina, resulting in stronger efficiency of transfection and gene expression in the RPE and PR layers, which has been undergoing in animal and clinical trials, however, the high technical operations are required. In recent years, as a new high-profile delivery route suprachorioidal injection of AAV vector can achieve more extensive transfection of target genes in the retina of rabbits and rats, which is less invasive than intravitreal and subretinal injection, Suprachorioidal injection is an important delivery route for future exploration of AAV vector mediated gene therapy for retinal diseases.
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- 1. Rodrigues GA, Shalaev E, Karami TK, et al. Pharmaceutical development of AAV-based gene therapy products for the eye[J]. Pharm Res, 2018, 36(2): 29. DOI: 10.1007/s11095-018-2554-7.
- 2. Carvalho LS, Vandenberghe LH. Promising and delivering gene therapies for vision loss[J]. Vision Res, 2015, 111(Pt B): 124-133. DOI: 10.1016/j.visres.2014.07.013.
- 3. 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.
- 4. Khabou H, Desrosiers M, Winckler C, et al. Insight into the mechanisms of enhanced retinal transduction by the engineered AAV2 capsid variant7m8[J]. Biotechnol Bioeng, 2016, 113(12): 2712-2724. DOI: 10.1002/bit.26031.
- 5. Bennett J, Wilson J, Sun D, et al. Adenovirus vector-mediated in vivo gene transfer into adult murine retina[J]. Invest Ophthalmol Vis Sci, 1994, 35(5): 2535-2542.
- 6. Wilmott P, Lisowski L, Alexander IE, et al. A user's guide to the inverted terminal repeats of adeno-associated virus[J]. Hum Gene Ther Methods, 2019, 30(6): 206-213. DOI: 10.1089/hgtb.2019.276.
- 7. Grosse S, Penaud-Budloo M, Herrmann AK, et al. Relevance of assembly-activating protein for adeno-associated virus vector production and capsid protein stability in mammalian and insect cells[J/OL]. J Virol, 2017, 91(20): e01198-e01117[2017-09-27]. https://pubmed.ncbi.nlm.nih.gov/28768875/. DOI: 10.1128/JVI.01198-17.
- 8. Duong TT, Lim J, Vasireddy V, et al. Comparative AAV-eGFP transgene expression using vector serotypes 1-9, 7m8, and 8b in human pluripotent stem cells, RPEs, and human and rat cortical neurons[J/OL]. Stem Cells Int, 2019, 2019: 7281912[2019-01-17]. https://pubmed.ncbi.nlm.nih.gov/30800164/. DOI: 10.1155/2019/7281912.
- 9. Hughes CP, O' Flynn NMJ, Gatherer M, et al. AAV2/8 anti-angiogenic gene therapy using single-chain antibodies inhibits murine choroidal neovascularization[J]. Mol Ther Methods Clin Dev, 2018, 13: 86-98. DOI: 10.1016/j.omtm.2018.11.005.
- 10. Duong TT, Vasireddy V, Ramachandran P, et al. Use of induced pluripotent stem cell models to probe the pathogenesis of choroideremia and to develop a potential treatment[J]. Stem Cell Res, 2018, 27: 140-150. DOI: 10.1016/j.scr.2018.01.009.
- 11. Hickey DG, Edwards TL, Barnard AR, et al. Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina[J]. Gene Ther, 2017, 24(12): 787-800. DOI: 10.1038/gt.2017.85.
- 12. Guziewicz KE, Zangerl B, Komaromy AM, et al. Recombinant AAV-mediated BEST1 transfer to the retinal pigment epithelium: analysis of serotype-dependent retinal effects[J/OL]. PLoS One, 2013, 8(10): 75666[2013-10-15]. https://pubmed.ncbi.nlm.nih.gov/24143172/. DOI: 10.1371/journal.pone.0075666.
- 13. De Silva SR, Charbel Issa P, Singh MS, et al. Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4(-/-) mouse and bipolar cells in the rd1 mouse and human retina ex vivo[J]. Gene Ther, 2016, 23(11): 767-774. DOI: 10.1038/gt.2016.54.
- 14. Katada Y, Kobayashi K, Tsubota K, et al. Evaluation of AAV-DJ vector for retinal gene therapy[J/OL]. Peer J, 2019, 7: 6317[2019-01-17]. https://pubmed.ncbi.nlm.nih.gov/30671314/. DOI: 10.7717/peerj.6317.
- 15. Mietzsch M, Jose A, Chipman P, et al. Completion of the AAV structural atlas: serotype capsid structures reveals clade-specific features[J]. Viruses, 2021, 13(1): 101. DOI: 10.3390/v13010101.
- 16. Puppo A, Cesi G, Marrocco E, et al. Retinal transduction profiles by high-capacity viral vectors[J]. Gene Ther, 2014, 21(10): 855-865. DOI: 10.1038/gt.2014.57.
- 17. Todorich B, Yiu G, Hahn P. Current and investigational pharmaco-therapeutic approaches for modulating retinal angiogenesis[J]. Expert Rev Clin Pharmacol, 2014, 7(3): 375-391. DOI: 10.1586/17512433.2014.890047.
- 18. Pavlou M, Schön C, Occelli LM, et al. Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders[J/OL]. EMBO Mol Med, 2021, 13(4): e13392[2021-04-09]. https://pubmed.ncbi.nlm.nih.gov/33616280/. DOI: 10.15252/emmm.202013392.
- 19. Chiha W, Bartlett CA, Petratos S, et al. Intravitreal application of AAV-BDNF or mutant AAV-CRMP2 protects retinal ganglion cells and stabilizes axons and myelin after partial optic nerve injury[J/OL]. Exp Neurol, 2020, 326: 113167[2020-01-02]. https://pubmed.ncbi.nlm.nih.gov/31904385/. DOI: 10.1016/j.expneurol.2019.113167.
- 20. Lee SHS, Kim HJ, Shin OK, et al. Intravitreal injection of AAV expressing soluble VEGF receptor-1 variant induces anti-VEGF activity and suppresses choroidal neovascularization[J]. Invest Ophthalmol Vis Sci, 2018, 59(13): 5398-5407. DOI: 10.1167/iovs.18-24926.
- 21. Crabtree E, Uribe K, Smith SM, et al. Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy[J/OL]. PLoS One, 2022, 17(8): e0270972[2022-08-18]. https://pubmed.ncbi.nlm.nih.gov/35980983/. DOI: 10.1371/journal.pone.0270972.
- 22. 李宗媛, 杨宁, 罗晋媛, 等. Krüppel样因子7对视网膜缺血再灌注损伤小鼠视网膜神经节细胞存活及视网膜电图的影响[J]. 中华眼底病杂志, 2020, 36(11): 846-852. DOI: 10.3760/cma.j.cn511434-20200602-00256.Li ZY, Yang N, Luo JY, et al. Effects of Krüppel-like factor 7 on the survival of retinal ganglion cells and electroretinogram after retinal ischemia-reperfusion injury[J]. Chin J Ocul Fundus Dis, 2020, 36(11): 846-852. DOI: 10.3760/cma.j.cn511434-20200602-00256.
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