Research progress of effect of different delivery routes of adeno-associated virus on retinal gene therapy_Chinese Journal of Ocular Fundus Diseases

Authors：

Wan Bo ¹ ,  Jin Zibing ²

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 100730, China;

Corresponding author：

Jin Zibing, Email: jinzibing@foxmail.com

Keywords：

Adeno-associated virus; Delivery route; Retinal gene therapy; Review

DOI：

10.3760/cma.j.cn511434-20230918-00391

Video：

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Abstract Full text Figures/Tables Video References Cited by

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. The delivery methods of AAV vector-mediated target genes to the retina inlucde intravitreal injection, subretinal injection, and suprachorioidal injection. 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. Subretinal injection of AAV vector can deliver the target gene to the local retina, resulting in stronger efficiency of transfection and gene expressio, 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. At present, the efficiency of AAV vector transduction in the retina is affected by the delivery mode. In the future, it is necessary to further explore the effect of AAV vector delivery mode on the transduction efficiency in order to find an important delivery route for mediating gene therapy for retinal diseases.

Citation： Wan Bo, Jin Zibing. Research progress of effect of different delivery routes of adeno-associated virus on retinal gene therapy. Chinese Journal of Ocular Fundus Diseases, 2024, 40(5): 409-414. doi: 10.3760/cma.j.cn511434-20230918-00391 Copy

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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.
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