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中华眼科医学杂志(电子版) ›› 2022, Vol. 12 ›› Issue (03) : 129 -133. doi: 10.3877/cma.j.issn.2095-2007.2022.03.001

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细胞基因疗法在视网膜退行性疾病中的应用和挑战
汪东生1, 吴理达2, 顾雨春2,()   
  1. 1. 100730 首都医科大学附属北京同仁医院 北京同仁眼科中心 眼科学与视觉科学北京市重点实验室
    2. 100176 北京呈诺医学科技有限公司
  • 收稿日期:2022-03-14 出版日期:2022-06-28
  • 通信作者: 顾雨春
  • 基金资助:
    国家重点基础研究发展规划项目(2013CB531206)

Application and challenges of cell and gene therapy in retinal degenerative diseases

Dongsheng Wang1, Lida Wu2, Yuchun Gu2,()   

  1. 1. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Science, Beijing 100730, China
    2. Allife Medical Science and Technology Co., Ltd., Beijing100176, China
  • Received:2022-03-14 Published:2022-06-28
  • Corresponding author: Yuchun Gu
引用本文:

汪东生, 吴理达, 顾雨春. 细胞基因疗法在视网膜退行性疾病中的应用和挑战[J]. 中华眼科医学杂志(电子版), 2022, 12(03): 129-133.

Dongsheng Wang, Lida Wu, Yuchun Gu. Application and challenges of cell and gene therapy in retinal degenerative diseases[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2022, 12(03): 129-133.

视网膜退行性疾病的治疗是多年困扰眼科临床工作者的棘手问题。细胞基因疗法(CGT)是国内外生物医药产业未来发展的主要方向之一。CGT产品运用了生物技术的前沿创新技术,这类产品给现阶段医学无法解决的疾病带来了极大的希望。CGT有望成为治疗视网膜退行性疾病的潜在疗法。本文中笔者总结和评述了CGT应用于视网膜退行性疾病的可行性和安全性,并进行相关信息的扩展。

The treatment of retinal degenerative diseases has been a thorny problem for ophthalmologists for many years. Cell and gene therapy (CGT) is one of the main directions for the future development of biomedical industry at home and abroad. The cutting-edge innovative biotechnology is used in CGT, which is great hopeful for the refractory diseases at this stage. CGT might be considered as a potential therapy for retinal degenerative diseases. The feasibility and safety of CGT in retinal degenerative diseases were summarized, and the relevant information of GCT were expanded in this paper.

表1 不同来源RPE移植治疗视网膜病变的临床研究
表2 不同血清型的AAV相关的临床试验
[1]
Mehat MS, Sundaram V, Ripamonti C, et al. Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration[J]. Ophthalmology, 2018, 125(11): 1765-1775.
[2]
Sachdeva MM, Eliott D. Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside[J]. Semin Ophthalmol, 2016, 31(1-2): 25-29.
[3]
Van Gelder RN, Chiang MF, Dyer MA, et al. Regenerative and restorative medicine for eye disease[J]. Nat Med, 2022, 28(6): 1149-1156.
[4]
Ruan GX, Barry E, Yu D, et al. CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10[J]. Mol Ther, 2017, 25(2): 331-341.
[5]
Sulek K. Nobel prize for Joshua Lederberg in 1958 for discovery of genetic recombination and organization of the hereditary material in bacteria. Prize for George W. Beadle and Edward L. Tatum for discovery of the regulatory effect of genes on biochemical processes[J]. Wiad Lek, 1969, 22(4): 418-420.
[6]
Dunbar CE, High KA, Joung JK, et al. Gene therapy comes of age[J]. Science, 2018, 359(6372): 4672.
[7]
Check E. Gene-therapy trials to restart following cancer risk review[J]. Nature, 2005, 434(7030): 127.
[8]
Friedmann T. A brief history of gene therapy[J]. Nat Genet, 1992, 2(2): 93-98.
[9]
McCune JM, Peault B, Streeter PR, et al. Preclinical evaluation of human hematolymphoid function in the SCID-hu mouse[J]. Immunol Rev, 1991, 124: 45-62.
[10]
Fischer A, Hacein-Bey-Abina S. Gene therapy for severe combined immunodeficiencies and beyond[J]. J Exp Med, 2020, 217(2): e20190607.
[11]
Sundaram V, Moore AT, Ali RR, et al. Retinal dystrophies and gene therapy[J]. Eur J Pediatr, 2012, 171(5): 757-765.
[12]
Kaufmann KB, Buning H, Galy A, et al. Gene therapy on the move[J]. EMBO Mol Med, 2013, 5(11): 1642-1661.
[13]
Maguire AM, Bennett J, Aleman EM, et al. Clinical Perspective: Treating RPE65-Associated Retinal Dystrophy[J]. Mol Ther, 2021, 29(2): 442-463.
[14]
Botto C, Dalkara D, El-Amraoui A. Progress in Gene Editing Tools and Their Potential for Correcting Mutations Underlying Hearing and Vision Loss[J]. Front Genome Ed, 2021, 3: 737632.
[15]
Lu JM, Zhang ZZ, Ma X, et al. Repression of microRNA-21 inhibits retinal vascular endothelial cell growth and angiogenesis via PTEN dependent-PI3K/Akt/VEGF signaling pathway in diabetic retinopathy[J]. Exp Eye Res, 2020, 190: 107886.
[16]
Hassall MM, Barnard AR, MacLaren RE. Gene Therapy for Color Blindness[J]. Yale J Biol Med, 2017, 90(4): 543-551.
[17]
Banskota S, Raguram A, Suh S, et al. Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins[J]. Cell, 2022, 185(2): 250-265.
[18]
Nazari H, Zhang L, Zhu D, et al. Stem cell based therapies for age-related macular degeneration: The promises and the challenges[J]. Prog Retin Eye Res, 2015, 48: 1-39.
[19]
Fischer MD, Michalakis S, Wilhelm B, et al. Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial[J]. JAMA Ophthalmol, 2020, 138(6): 643-651.
[20]
da Cruz L, Fynes K, Georgiadis O, et al. Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration[J]. Nat Biotechnol, 2018, 36(4): 328-337.
[21]
Mandai M, Watanabe A, Kurimoto Y, et al. Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration[J]. N Engl J Med, 2017, 376(11): 1038-1046.
[22]
Sharma R, Khristov V, Rising A, et al. Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs[J]. Sci Transl Med, 2019, 11(475): 5580.
[23]
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.
[24]
Li Y, Chan L, Nguyen HV, et al. Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC-Derived Retinal Pigment Epithelium Cells[J]. Adv Exp Med Biol, 2016, 854: 549-555.
[25]
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.
[26]
Arnhold S, Absenger Y, Klein H, et al. Transplantation of bone marrow-derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse[J]. Graefes Arch Clin Exp Ophthalmol, 2007, 245(3): 414-422.
[27]
Inoue Y, Iriyama A, Ueno S, et al. Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration[J]. Exp Eye Res, 2007, 85(2): 234-241.
[28]
Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies[J]. Lancet, 2015, 385(9967): 509-516.
[29]
Song WK, Park KM, Kim HJ, et al. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients[J]. Stem Cell Reports, 2015, 4(5): 860-872.
[30]
Shim SH, Kim G, Lee DR, et al. Survival of Transplanted Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Human Recipient for 22 Months[J]. JAMA Ophthalmol, 2017, 135(3): 287-289.
[31]
Wang L, Wu W, Gu Q, et al. The effect of clinical-grade retinal pigment epithelium derived from human embryonic stem cells using different transplantation strategies[J]. Protein Cell, 2019, 10(6): 455-460.
[32]
Liu Y, Xu HW, Wang L, et al. Human embryonic stem cell-derived retinal pigment epithelium transplants as a potential treatment for wet age-related macular degeneration[J]. Cell Discov, 2018, 4: 50.
[33]
Fahim A. Retinitis pigmentosa: recent advances and future directions in diagnosis and management[J]. Curr Opin Pediatr, 2018, 30(6): 725-733.
[34]
Tsang SH, Sharma T. Retinitis Pigmentosa (Non-syndromic)[J]. Adv Exp Med Biol, 2018, 1085: 125-130.
[35]
Sudharsan R, Beltran WA. Progress in Gene Therapy for Rhodopsin Autosomal Dominant Retinitis Pigmentosa[J]. Adv Exp Med Biol, 2019, 1185: 113-118.
[36]
Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, et al. Current Clinical Applications of In Vivo Gene Therapy with AAVs[J]. Mol Ther, 2021, 29(2): 464-488.
[37]
Darrow JJ. Luxturna: FDA documents reveal the value of a costly gene therapy[J]. Drug Discov Today, 2019, 24(4): 949-954.
[38]
Keeler AM, Flotte TR. Recombinant Adeno-Associated Virus Gene Therapy in Light of Luxturna (and Zolgensma and Glybera): Where Are We, and How Did We Get Here?[J]. Annu Rev Virol, 2019, 6(1): 601-621.
[39]
Maeder ML, Stefanidakis M, Wilson CJ, et al. Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10[J]. Nat Med, 2019, 25(2): 229-233.
[40]
Russell SR, Drack AV, Cideciyan AV, et al. Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial[J]. Nat Med, 2022, 28(5): 1014-1021.
[41]
Kachi S, Binley K, Yokoi K, et al. Equine infectious anemia viral vector-mediated codelivery of endostatin and angiostatin driven by retinal pigmented epithelium-specific VMD2 promoter inhibits choroidal neovascularization[J]. Hum Gene Ther, 2009, 20(1): 31-39.
[42]
Yang Y, Liu Y, Li Y, et al. MicroRNA-15b Targets VEGF and Inhibits Angiogenesis in Proliferative Diabetic Retinopathy[J]. J Clin Endocrinol Metab, 2020, 105(11): 3404-3415.
[43]
Han N, Xu H, Yu N, et al. MiR-203a-3p inhibits retinal angiogenesis and alleviates proliferative diabetic retinopathy in oxygen-induced retinopathy (OIR) rat model via targeting VEGFA and HIF-1alpha[J]. Clin Exp Pharmacol Physiol, 2020, 47(1): 85-94.
[44]
Zhang H, Su B, Jiao L, et al. Transplantation of GMP-grade human iPSC-derived retinal pigment epithelial cells in rodent model: the first pre-clinical study for safety and efficacy in China[J]. Ann Transl Med, 2021, 9(3): 245.
[45]
Sahel JA, Dalkara D. Gene therapy for retinal dystrophy[J]. Nat Med, 2019, 25(2): 198-199.
[46]
Mingozzi F, High KA. Immune responses to AAV vectors: overcoming barriers to successful gene therapy[J]. Blood, 2013, 122(1): 23-36.
[47]
McClements ME, Barnard AR, Singh MS, et al. An AAV Dual Vector Strategy Ameliorates the Stargardt Phenotype in Adult Abca4 Mice[J]. Hum Gene Ther, 2019, 30(5): 590-600.
[48]
Escors D, Breckpot K. Lentiviral vectors in gene therapy: their current status and future potential[J]. Arch Immunol Ther Exp (Warsz), 2010, 58(2): 107-119.
[49]
Liu L, Yang J, Men K, et al. Current Status of Nonviral Vectors for Gene Therapy in China[J]. Hum Gene Ther, 2018, 29(2): 110-120.
[50]
Verdera HC, Kuranda K, Mingozzi F. AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer[J]. Mol Ther, 2020, 28(3): 723-746.
[51]
Wu Z, Asokan A, Samulski RJ. Adeno-associated virus serotypes: vector toolkit for human gene therapy[J]. Mol Ther, 2006, 14(3): 316-327.
[52]
Quinn J, Musa A, Kantor A, et al. Genome-Editing Strategies for Treating Human Retinal Degenerations[J]. Hum Gene Ther, 2021, 32(5-6): 247-259.
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