Results and possible prospects of genetic technology in ophthalmology (literature review). Part 2.

Authors

  • N. A. Gavrilova A.I. Evdokimov Moscow State University of Medicine and Dentistry; Moscow (Russian Federation)
  • O. Ie. Tishchenko A.I. Evdokimov Moscow State University of Medicine and Dentistry; Moscow (Russian Federation)
  • A. V. Zinov’eva A.I. Evdokimov Moscow State University of Medicine and Dentistry; Moscow (Russian Federation)

DOI:

https://doi.org/10.31288/oftalmolzh202124045

Keywords:

small interfering RNAs, antisense nucleotides, CRISPR, gene therapy, retina

Abstract

The emergence of fundamentally novel technological solutions in the field of gene therapy today, the formation of the priority and the development of genetic technologies create serious prerequisites for the beginning of a new Fusion era in ophthalmology in the near future. This review, in its second part, presents the results of fundamental and clinical studies on the use of genetic therapeutic strategies – gene replacement, gene suppression, genomic editing using CRISPR / Cas9 technology which have been used in ophthalmology over the past several years.

References

1.Ali RR, Sarra GM, Stephens C, Alwis MD, Bainbridge JW, Munro PM, et al. Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat Genet. 2000;25(3):306‐10. https://doi.org/10.1038/77068

2.Vollrath D, Feng W, Duncan JL, Yasumura D, D'Cruz PM, Chappelow A, et al. Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci USA. 2001;98(22):12584‐9. https://doi.org/10.1073/pnas.221364198

3.Smith AJ, Schlichtenbrede FC, Tschernutter M, Bainbridge JW, Thrasher AJ, Ali RR. AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa. Mol Ther. 2003;8(2):188‐95. https://doi.org/10.1016/S1525-0016(03)00144-8

4.Tschernutter M, Schlichtenbrede FC, Howe S, Balaggan KS, Munro PM, Bainbridge JWB, et al. Long‐term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus‐mediated gene therapy. Gene Ther. 2005;12694-701. https://doi.org/10.1038/sj.gt.3302460

5.Bennicelli J, Wright JF, Komaromy A, Jacobs JB, Hauck B, Zelenaia O, et al. Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer. Mol Ther. 2008;16(3):458‐465. https://doi.org/10.1038/sj.mt.6300389

6.Allocca M, Doria M, Petrillo M, Colella P, Garcia-Hoyos M, Gibbs D, et al. Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice. J Clin Invest. 2008;118(5):1955‐1964. https://doi.org/10.1172/JCI34316

7.Drenser KA, Timmers AM, Hauswirth WW, Lewin AS. Ribozyme-targeted destruction of RNA associated with autosomal-dominant retinitis pigmentosa 5. Invest Ophthalmol Vis Sci. 1998;39:681-9.

8.Lewin AS, Drenser KA, Hauswirth WW, Nishikawa S, Yasumura D, Flannery JG, LaVail MM. Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa 4. Nat Med. 1998;4:967-71. https://doi.org/10.1038/nm0898-967

9.O'Neill B, Millington-Ward S, O'Reilly M, Tuohy G, Kiang AS, Kenna PF, et al. Ribozyme-based therapeutic approaches for autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2000;41(10):2863‐2869.

10.Sullivan JM, Pietras KM, Shin BJ, Misasi JN. Hammerhead ribozymes designed to cleave all human rod opsin mRNAs which cause autosomal dominant retinitis pigmentosa 1. Mol Vis. 2002;8:102-13.

11.Gorbatyuk MS, Pang JJ, Thomas J Jr., Hauswirth WW, Lewin AS. Knockdown of wild-type mouse rhodopsin using an AAV vectored ribozyme as part of an RNA replacement approach. MolVis. 2005;11:648-56.

12.Gorbatyuk M, Justilien V, Liu J, Hauswirth WW, Lewin AS. Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Exp Eye Res. 2007;84(1):44‐52. https://doi.org/10.1016/j.exer.2006.08.014

13.Corydon TJ. Antiangiogenic Eye Gene Therapy. Human Gene Therapy. 2015;26(8):525-37. https://doi.org/10.1089/hum.2015.064

14.Garba AO, Mousa SA. Bevasiranib for the treatment of wet, age-related macular degeneration. Ophthalmol Eye Dis. 2010;2:75-83. https://doi.org/10.4137/OED.S4878

15.Guzman-Aranguez A, Loma P, Pintor J. Small-interfering RNAs (siRNAs) as a promising tool for ocular therapy. Br J Pharmacol. 2013;170(4):730-47. https://doi.org/10.1111/bph.12330

16.Nguyen QD, Schachar RA, Nduaka CI, Sperling M, Klamerus KJ, Chi-Burris K, et al; MONET Clinical Study Group. Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study). Ophthalmology. 2012;119(9):1867-73. https://doi.org/10.1016/j.ophtha.2012.03.043

17.Chau VQ, Hu J, Gong X, Hulleman JD, Ufret-Vincenty RL, Rigo F, et al. Delivery of Antisense Oligonucleotides to the Cornea. Nucleic Acid Therapeutics. 2020; https://doi.org/10.1089/nat.2019.0838

18.Cideciyan AV, Jacobson SG, Drack AV, Ho AC, Charng J, Garafalo AV, et al. Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect. Nat Med. 2019;25(2):225-8. https://doi.org/10.1038/s41591-018-0295-0

19.Collin RW, Garanto A. Applications of antisense oligonucleotides for the treatment of inherited retinal diseases. Curr Opin Ophthalmol. 2017;28(3):260-6. https://doi.org/10.1097/ICU.0000000000000363

20.Gerard X, Garanto A, Rozet JM, Collin R.W. Antisense Oligonucleotide Therapy for Inherited Retinal Dystrophies. Adv Exp Med Biol. 2016;854:517‐24. https://doi.org/10.1007/978-3-319-17121-0_69

21.Hu J, Rong Z, Gong X, Zhou Z, Sharma VK, Xing C, et al. Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy. Hum Mol Genet. 2018;27(6):1015-26. https://doi.org/10.1093/hmg/ddy018

22.Hu J, Shen X, Rigo F, Prakash TP, Mootha VV, Corey DR. Duplex RNAs and ss-siRNAs Block RNA Foci Associated with Fuchs' Endothelial Corneal Dystrophy. Nucleic Acid Ther. 2019;29(2):73‐81. https://doi.org/10.1089/nat.2018.0764

23.Moore SM, Skowronska-Krawczyk D, Chao DL. Emerging Concepts for RNA Therapeutics for Inherited Retinal Disease. Adv Exp Med Biol. 2019;1185:85‐89. https://doi.org/10.1007/978-3-030-27378-1_14

24.Rocha EM, Nominato LF, Reinach PS. Re: Cursiefen et al.: Aganirsen antisense oligonucleotide eye drops inhibit keratitis-induced corneal neovascularization and reduce need for transplantation: the I-CAN study. Ophthalmology. 2015;122(5):e28. https://doi.org/10.1016/j.ophtha.2014.10.017

25.Sangermano R, Garanto A, Khan M, Runhart EH, Bauwens M, Bax NM, et al. Deep-intronic ABCA4 variants explain missing heritability in Stargardt disease and allow correction of splice defects by antisense oligonucleotides. Genet Med. 2019;21(8):1751-60. https://doi.org/10.1038/s41436-018-0414-9

26.Yang G, Fu Y, Zhang L, Lu X, Li Q. miR106b regulates retinoblastoma Y79 cells through Runx3. Oncol Rep. 2017;38(5):3039-43. https://doi.org/10.3892/or.2017.5931

27.Zarouchlioti C, Sanchez-Pintado B, Hafford Tear NJ, et al. Antisense Therapy for a Common Corneal Dystrophy Ameliorates TCF4 Repeat Expansion-Mediated Toxicity. Am J Hum Genet. 2018;102(4):528-39. https://doi.org/10.1016/j.ajhg.2018.02.010

28.Cursiefen C, Viaud E, Bock F, Geudelin B, Ferry A, Kadlecová P, Lévy M, et al. Aganirsen antisense oligonucleotide eye drops inhibit keratitis-induced corneal neovascularization and reduce need for transplantation: the I-CAN study. Ophthalmology. 2014;121(9):1683‐92. https://doi.org/10.1016/j.ophtha.2014.03.038

29.Lorenz K, Scheller Y, Bell K, Grus F, Ponto KA, Bock F, et al. A prospective, randomised, placebo-controlled, double-masked, three-armed, multicentre phase II/III trial for the Study of a Topical Treatment of Ischaemic Central Retinal Vein Occlusion to Prevent Neovascular Glaucoma - the STRONG study: study protocol for a randomised controlled trial. Trials. 2017;18(1):128. https://doi.org/10.1186/s13063-017-1861-3

30.Pfeiffer N, Voykov B, Renieri G, Bell K, Richter P, Weigel M, et al. First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery. PLoS One. 2017;12(11):e0188899. https://doi.org/10.1371/journal.pone.0188899

31.Naert T, Colpaert R, Van Nieuwenhuysen T, Dimitrakopoulou D, Leoen J, Haustraete J, et al. CRISPR/Cas9 mediated knockout of rb1 and rbl1 leads to rapid and penetrant retinoblastoma development in Xenopus tropicalis. Sci Rep. 2016;6:35264. https://doi.org/10.1038/srep35264

32.Wu WH, Tsai YT, Justus S, Lee TT, Zhang L, Lin CS, et al. CRISPR Repair Reveals Causative Mutation in a Preclinical Model of Retinitis Pigmentosa. Mol Ther. 2016;24(8):1388-94. https://doi.org/10.1038/mt.2016.107

33.Bakondi B, Lv W, Lu B, Jones MK, Tsai Y, Kim KJ, et al. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa. Mol Ther. 2016;24(3):556‐63. https://doi.org/10.1038/mt.2015.220

34.Burnight ER, Giacalone JC, Cooke JA, Thompson JR, Bohrer LR, Chirco KR, et al. CRISPR-Cas9 genome engineering: Treating inherited retinal degeneration. Prog Retin Eye Res. 2018;65:28‐49. https://doi.org/10.1016/j.preteyeres.2018.03.003

35.Huang KC, Wang ML, Chen SJ, Kuo JC, Wang WJ, Nhi Nguyen PN, et al. Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis. Stem Cell Reports. 2019;13(5):906-23. https://doi.org/10.1016/j.stemcr.2019.09.010

36.Kim EK, Kim S, Maeng YS. Generation of TGFBI knockout ABCG2+/ABCB5+ double-positive limbal epithelial stem cells by CRISPR/Cas9-mediated genome editing. PLoS One. 2019;14(2):e0211864. https://doi.org/10.1371/journal.pone.0211864

37.Kim K, Park SW, Kim JH, Lee SH, Kim D, Koo T, et al. Genome surgery using Cas9 ribonucleoproteins for the treatment of age-related macular degeneration. Genome Res. 2017;27(3):419‐426. https://doi.org/10.1101/gr.219089.116

38.Peddle CF, MacLaren RE The Application of CRISPR/Cas9 for the Treatment of Retinal Diseases. Yale J Biol Med. 2017;90(4):533‐41.

39.Ruan GX, Barry E, Yu D, Lukason M, Cheng SH, Scaria A. CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10. Mol Ther. 2017;25(2):331‐41. https://doi.org/10.1016/j.ymthe.2016.12.006

40.Suzuki K, Tsunekawa Y, Hernandez-Benitez R, Wu J, Zhu J, Kim EJ, et al. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature. 2016;540(7631):144‐9. https://doi.org/10.1038/nature20565

41.Taketani Y, Kitamoto K, Sakisaka T, Kimakura M, Toyono T, Yamagami S, et al. Repair of the TGFBI gene in human corneal keratocytes derived from a granular corneal dystrophy patient via CRISPR/Cas9-induced homology-directed repair. Sci Rep. 2017;7(1):16713. https://doi.org/10.1038/s41598-017-16308-2

42.Xu CL, Park KS, Tsang SH. CRISPR/Cas9 genome surgery for retinal diseases. Drug Discov Today Technol. 2018;28:23‐32. https://doi.org/10.1016/j.ddtec.2018.05.001

43.Yu W, Mookherjee S, Chaitankar V, Suja Hiriyanna, Kim J-W, Brooks M, Ataeijannati Y, et al. Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice. Nat Commun. 2017;8:14716. https://doi.org/10.1038/ncomms14716

44.Zhu J, Ming C, Fu X, Duan Y, Hoang DA, Rutgard J, Zhang R, et al. Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors. Cell Res. 2017;27:830-3. https://doi.org/10.1038/cr.2017.57

45.Chung SH, Mollhoff IN, Nguyen U, Nguyen A, Stucka N, Tieu E, et al. Factors Impacting Efficacy of AAV-Mediated CRISPR-Based Genome Editing for Treatment of Choroidal Neovascularization. Mol Ther Methods Clin Dev. 2020;17:409‐17. https://doi.org/10.1016/j.omtm.2020.01.006

46.Huang X, Zhou G, Wu W, Duan Y, Ma G, Song J, et al. Genome editing abrogates angiogenesis in vivo. Nat Commun. 2017;8(1):112. https://doi.org/10.1038/s41467-017-00140-3

47.Yiu G, Tieu E, Nguyen AT, Wong B, Smit-McBride Z. Genomic Disruption of VEGF-A Expression in Human Retinal Pigment Epithelial Cells Using CRISPR-Cas9 Endonuclease. Invest Ophthalmol Vis Sci. 2016;57(13):5490-7. https://doi.org/10.1167/iovs.16-20296

48.Lightfoot JD, Fuller KK. CRISPR/Cas9-Mediated Gene Replacement in the Fungal Keratitis Pathogen Fusarium solani var. petroliphilum. Microorganisms. 2019;7(10):457. https://doi.org/10.3390/microorganisms7100457

49.Yang TC, Chang CY, Yarmishyn AA, Mao YS, Yang YP, Wang ML, et al. Carboxylated nanodiamond-mediated CRISPR-Cas9 delivery of human retinoschisis mutation into human iPSCs and mouse retina. Acta Biomater. 2020;101:484-94. https://doi.org/10.1016/j.actbio.2019.10.037

50.Li F, Hung SSC, Mohd Khalid MKN, Wang J-H, Chrysostomou V, Wong VHY, et al. Utility of Self-Destructing CRISPR/Cas Constructs for Targeted Gene Editing in the Retina. Hum Gene Ther. 2019;30(11):1349‐60. https://doi.org/10.1089/hum.2019.021

51.Schaefer KA, Wu WH, Colgan DF, Tsang SH, Bassuk AG, Mahajan VB. Unexpected mutations after CRISPR-Cas9 editing in vivo. Nat Methods. 2017;14(6):547‐48. https://doi.org/10.1038/nmeth.4293

52.Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149-57. https://doi.org/10.1038/s41586-019-1711-4

53.Hernandez M, Recalde S, Garcia-Garcia L, Bezunartea J, Miskey C, Johnen S, Diarra S, et al. Preclinical Evaluation of a Cell-Based Gene Therapy Using the Sleeping Beauty Transposon System in Choroidal Neovascularization. Mol Ther Methods Clin Dev. 2019;15:403-17. https://doi.org/10.1016/j.omtm.2019.10.013

Published

2025-09-19

How to Cite

[1]
Gavrilova, N.A. et al. 2025. Results and possible prospects of genetic technology in ophthalmology (literature review). Part 2. Journal of Ophthalmology (Ukraine). 2 (Sep. 2025), 40–45. DOI:https://doi.org/10.31288/oftalmolzh202124045.

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