Zephyrnet Logo

Genome editing in the treatment of ocular diseases – Experimental & Molecular Medicine

Date:

  • Porteus, M. H. A new class of medicines through DNA editing. N. Engl. J. Med. 380, 947–959 (2019).

    Article  CAS  PubMed  Google Scholar 

  • Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38, 824–844 (2020).

    Article  CAS  PubMed  Google Scholar 

  • Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816–821 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doudna, J. A. & Charpentier, E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096 (2014).

    Article  PubMed  Google Scholar 

  • Wang, J. Y. & Doudna, J. A. CRISPR technology: a decade of genome editing is only the beginning. Science 379, eadd8643 (2023).

    Article  CAS  PubMed  Google Scholar 

  • Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420–424 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gaudelli, N. M. et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551, 464–471 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Newby, G. A. & Liu, D. R. In vivo somatic cell base editing and prime editing. Mol. Ther. 29, 3107–3124 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rees, H. A. & Liu, D. R. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19, 770–788 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, P. J. & Liu, D. R. Prime editing for precise and highly versatile genome manipulation. Nat. Rev. Genet. 24, 161–177 (2023).

    Article  CAS  PubMed  Google Scholar 

  • Caruso, S. M., Quinn, P. M., da Costa, B. L. & Tsang, S. H. CRISPR/Cas therapeutic strategies for autosomal dominant disorders. J. Clin. Invest. 132, e158287 (2022).

  • Suh, S., Choi, E. H., Raguram, A., Liu, D. R. & Palczewski, K. Precision genome editing in the eye. Proc. Natl Acad. Sci. USA 119, e2210104119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan, A. L., Du, S. W. & Palczewski, K. Genome editing, a superior therapy for inherited retinal diseases. Vis. Res. 206, 108192 (2023).

    Article  PubMed  Google Scholar 

  • Du, S. W. & Palczewski, K. Eye on genome editing. J. Exp. Med. 220, e20230146 (2023).

  • Palczewska, G. et al. Noninvasive multiphoton fluorescence microscopy resolves retinol and retinal condensation products in mouse eyes. Nat. Med. 16, 1444–1449 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palczewska, G. et al. Noninvasive two-photon microscopy imaging of mouse retina and retinal pigment epithelium through the pupil of the eye. Nat. Med. 20, 785–789 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palczewska, G. et al. Noninvasive two-photon optical biopsy of retinal fluorophores. Proc. Natl Acad. Sci. USA 117, 22532–22543 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boguslawski, J. et al. In vivo imaging of the human eye using a 2-photon-excited fluorescence scanning laser ophthalmoscope. J. Clin. Invest. 132, e154218 (2022).

  • Palczewska, G., Wojtkowski, M. & Palczewski, K. From mouse to human: accessing the biochemistry of vision in vivo by two-photon excitation. Prog. Retin. Eye Res. 93, 101170 (2023).

    Article  CAS  PubMed  Google Scholar 

  • Ishino, Y., Shinagawa, H., Makino, K., Amemura, M. & Nakata, A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J. Bacteriol. 169, 5429–5433 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mojica, F. J., Díez-Villaseñor, C., Soria, E. & Juez, G. Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol. Microbiol. 36, 244–246 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Jansen, R., Embden, J. D., Gaastra, W. & Schouls, L. M. Identification of genes that are associated with DNA repeats in prokaryotes. Mol. Microbiol. 43, 1565–1575 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Mojica, F. J., Diez-Villasenor, C., Garcia-Martinez, J. & Soria, E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J. Mol. Evol. 60, 174–182 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Bolotin, A., Quinquis, B., Sorokin, A. & Ehrlich, S. D. Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151, 2551–2561 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Pourcel, C., Salvignol, G. & Vergnaud, G. CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology 151, 653–663 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Barrangou, R. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709–1712 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Makarova, K. S., Grishin, N. V., Shabalina, S. A., Wolf, Y. I. & Koonin, E. V. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol. Direct 1, 7 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  • Makarova, K. S. et al. Evolution and classification of the CRISPR–Cas systems. Nat. Rev. Microbiol. 9, 467–477 (2011).

    Article  CAS  PubMed  Google Scholar 

  • van der Oost, J., Westra, E. R., Jackson, R. N. & Wiedenheft, B. Unravelling the structural and mechanistic basis of CRISPR–Cas systems. Nat. Rev. Microbiol. 12, 479–492 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  • Gasiunas, G., Barrangou, R., Horvath, P. & Siksnys, V. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc. Natl Acad. Sci. USA 109, E2579–E2586 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ceccaldi, R., Rondinelli, B. & D’Andrea, A. D. Repair pathway choices and consequences at the double-strand break. Trends Cell Biol. 26, 52–64 (2016).

    Article  CAS  PubMed  Google Scholar 

  • Carroll, D. Genome engineering with targetable nucleases. Annu. Rev. Biochem. 83, 409–439 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Doudna, J. A. & Charpentier, E. The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096 (2014).

    Article  PubMed  Google Scholar 

  • Maruyama, T. et al. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat. Biotechnol. 33, 538–542 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Musunuru, K. et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 593, 429–434 (2021).

    Article  CAS  PubMed  Google Scholar 

  • Koblan, L. W. et al. Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat. Biotechnol. 36, 843–846 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38, 824–844 (2020).

    Article  CAS  PubMed  Google Scholar 

  • Lin, Q. et al. Prime genome editing in rice and wheat. Nat. Biotechnol. 38, 582–585 (2020).

    Article  CAS  PubMed  Google Scholar 

  • Nishimasu, H. et al. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 156, 935–949 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang, F. & Doudna, J. A. CRISPR–Cas9 structures and mechanisms. Annu. Rev. Biophys. 46, 505–529 (2017).

    Article  CAS  PubMed  Google Scholar 

  • Nishida, K. et al. Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 353, aaf8729 (2016).

  • Li, X. et al. Base editing with a Cpf1-cytidine deaminase fusion. Nat. Biotechnol. 36, 324–327 (2018).

    Article  CAS  PubMed  Google Scholar 

  • Song, Y. et al. Large-fragment deletions induced by Cas9 cleavage while not in the BEs system. Mol. Ther. Nucleic Acids 21, 523–526 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Komor, A. C., Badran, A. H. & Liu, D. R. CRISPR-based technologies for the manipulation of eukaryotic genomes. Cell 168, 20–36 (2017).

    Article  CAS  PubMed  Google Scholar 

  • Ryu, S.-M. et al. Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy. Nat. Biotechnol. 36, 536–539 (2018).

    Article  CAS  PubMed  Google Scholar 

  • Suh, S. et al. Restoration of visual function in adult mice with an inherited retinal disease via adenine base editing. Nat. Biomed. Eng. 5, 169–178 (2021).

    Article  CAS  PubMed  Google Scholar 

  • Koblan, L. W. et al. In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice. Nature 589, 608–614 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Newby, G. A. et al. Base editing of haematopoietic stem cells rescues sickle cell disease in mice. Nature 595, 295–302 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi, E. H. et al. In vivo base editing rescues cone photoreceptors in a mouse model of early-onset inherited retinal degeneration. Nat. Commun. 13, 1830 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reichart, D. et al. Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice. Nat. Med. 29, 412–421 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Komor, A. C. et al. Improved base excision repair inhibition and bacteriophage Mu Gam protein yields C:G-to-T:A base editors with higher efficiency and product purity. Sci. Adv. 3, eaao4774 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  • Zafra, M. P. et al. Optimized base editors enable efficient editing in cells, organoids and mice. Nat. Biotechnol. 36, 888–893 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richter, M. F. et al. Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat. Biotechnol. 38, 883–891 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller, S. M., Wang, T. & Liu, D. R. Phage-assisted continuous and non-continuous evolution. Nat. Protoc. 15, 4101–4127 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gaudelli, N. M. et al. Directed evolution of adenine base editors with increased activity and therapeutic application. Nat. Biotechnol. 38, 892–900 (2020).

    Article  CAS  PubMed  Google Scholar 

  • Jin, S. et al. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science 364, 292 (2019).

    Article  CAS  PubMed  Google Scholar 

  • Zuo, E. et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 364, 289–292 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao, R. et al. Genomic and transcriptomic analyses of prime editing guide RNA–independent off-target effects by prime editors. CRISPR J. 5, 276–293 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Park, S.-J. et al. Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor. Genome Biol. 22, 170 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  • Velimirovic, M. et al. Peptide fusion improves prime editing efficiency. Nat. Commun. 13, 3512 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song, M. et al. Generation of a more efficient prime editor 2 by addition of the Rad51 DNA-binding domain. Nat. Commun. 12, 5617 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson, J. W. et al. Engineered pegRNAs improve prime editing efficiency. Nat. Biotechnol. 40, 402–410 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Zhang, G. et al. Enhancement of prime editing via xrRNA motif-joined pegRNA. Nat. Commun. 13, 1856 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anzalone, A. V. et al. Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing. Nat. Biotechnol. 40, 731–740 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Liu, N. et al. HDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing. Mol. Ther. Nucleic Acids 29, 36–46 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, P. J. et al. Enhanced prime editing systems by manipulating cellular determinants of editing outcomes. Cell 184, 5635–5652.e5629 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kevany, B. M. & Palczewski, K. Phagocytosis of retinal rod and cone photoreceptors. Physiology 25, 8–15 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Kiser, P. D. & Palczewski, K. Retinoids and retinal diseases. Annu. Rev. Vis. Sci. 2, 197–234 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  • Flaxman, S. R. et al. Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. Lancet Glob. Health 5, e1221–e1234 (2017).

    Article  PubMed  Google Scholar 

  • Taylor, A. Ocular immune privilege. Eye 23, 1885–1889 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Streilein, J. W. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat. Rev. Immunol. 3, 879–889 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Sapino, S. et al. Ocular drug delivery: a special focus on the thermosensitive approach. Nanomaterials 9, 884 (2019).

  • Dias, M. F. et al. Molecular genetics and emerging therapies for retinitis pigmentosa: basic research and clinical perspectives. Prog. Retin. Eye Res. 63, 107–131 (2018).

    Article  CAS  PubMed  Google Scholar 

  • Kumar, S. et al. RNA-targeting strategies as a platform for ocular gene therapy. Prog. Retin. Eye Res. 92, 101110 (2023).

    Article  CAS  PubMed  Google Scholar 

  • Jo, D. H., Bae, S., Kim, H. H., Kim, J. S. & Kim, J. H. In vivo application of base and prime editing to treat inherited retinal diseases. Prog. Retin. Eye Res. 94, 101132 (2023).

  • Russell, S. et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet 390, 849–860 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bainbridge, J. W. et al. Long-term effect of gene therapy on Leber’s congenital amaurosis. N. Engl. J. Med. 372, 1887–1897 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  • Jacobson, S. G. et al. Improvement and decline in vision with gene therapy in childhood blindness. N. Engl. J. Med. 372, 1920–1926 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cideciyan, A. V. et al. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc. Natl Acad. Sci. USA 110, E517–E525 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gardiner, K. L. et al. Long-term structural outcomes of late-stage RPE65 gene therapy. Mol. Ther. 28, 266–278 (2020).

    Article  CAS  PubMed  Google Scholar 

  • Eghrari, A. O., Riazuddin, S. A. & Gottsch, J. D. Overview of the cornea: structure, function, and development. Prog. Mol. Biol. Transl. Sci. 134, 7–23 (2015).

  • Meek, K. M., Dennis, S. & Khan, S. Changes in the refractive index of the stroma and its extrafibrillar matrix when the cornea swells. Biophys. J. 85, 2205–2212 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liesegang, T. J. Herpes simplex virus epidemiology and ocular importance. Cornea 20, 1–13 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Iliff, B. W., Riazuddin, S. A. & Gottsch, J. D. The genetics of Fuchs’ corneal dystrophy. Expert Rev. Ophthalmol. 7, 363–375 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Munier, F. L. et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nat. Genet. 15, 247–251 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Farooq, A. V. & Shukla, D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv. Ophthalmol. 57, 448–462 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  • Weerasooriya, S., DiScipio, K. A., Darwish, A. S., Bai, P. & Weller, S. K. Herpes simplex virus 1 ICP8 mutant lacking annealing activity is deficient for viral DNA replication. Proc. Natl Acad. Sci. USA 116, 1033–1042 (2019).

    Article  CAS  PubMed  Google Scholar 

  • Weller, S. K. & Coen, D. M. Herpes simplex viruses: mechanisms of DNA replication. Cold Spring Harb. Perspect. Biol. 4, a013011 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  • Yin, D. et al. Targeting herpes simplex virus with CRISPR-Cas9 cures herpetic stromal keratitis in mice. Nat. Biotechnol. 39, 567–577 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei, A. et al. In vivo CRISPR gene editing in patients with herpes stromal keratitis. Preprint at medRxiv https://doi.org/10.1101/2023.02.21.23285822 (2023).

  • Gottsch, J. D. et al. Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of Fuchs corneal dystrophy. Invest. Ophthalmol. Vis. Sci. 46, 1934–1939 (2005).

    Article  PubMed  Google Scholar 

  • Biswas, S. et al. Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy. Hum. Mol. Genet. 10, 2415–2423 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Jun, A. S. et al. An alpha 2 collagen VIII transgenic knock-in mouse model of Fuchs endothelial corneal dystrophy shows early endothelial cell unfolded protein response and apoptosis. Hum. Mol. Genet. 21, 384–393 (2012).

    Article  CAS  PubMed  Google Scholar 

  • Meng, H. et al. L450W and Q455K Col8a2 knock-in mouse models of Fuchs endothelial corneal dystrophy show distinct phenotypes and evidence for altered autophagy. Invest. Ophthalmol. Vis. Sci. 54, 1887–1897 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  • Uehara, H. et al. Start codon disruption with CRISPR/Cas9 prevents murine Fuchs’ endothelial corneal dystrophy. Elife 10, e55637 (2021).

  • Lakshminarayanan, R. et al. Clinical and genetic aspects of the TGFBI-associated corneal dystrophies. Ocul. Surf. 12, 234–251 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Akiya, S., Takahashi, H., Nakano, N., Hirose, N. & Tokuda, Y. Granular-lattice (Avellino) corneal dystrophy. Ophthalmologica 213, 58–62 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Folberg, R. et al. Clinically atypical granular corneal dystrophy with pathologic features of lattice-like amyloid deposits. A study of these families. Ophthalmology 95, 46–51 (1988).

    Article  CAS  PubMed  Google Scholar 

  • Moon, J. W. et al. Homozygous granular corneal dystrophy type II (Avellino corneal dystrophy): natural history and progression after treatment. Cornea 26, 1095–1100 (2007).

    Article  PubMed  Google Scholar 

  • Watanabe, H. et al. Two patterns of opacity in corneal dystrophy caused by the homozygous BIG-H3 R124H mutation. Am. J. Ophthalmol. 132, 211–216 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Dinh, R., Rapuano, C. J., Cohen, E. J. & Laibson, P. R. Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy. Ophthalmology 106, 1490–1497 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Lyons, C. J. et al. Granular corneal dystrophy. Visual results and pattern of recurrence after lamellar or penetrating keratoplasty. Ophthalmology 101, 1812–1817 (1994).

    Article  CAS  PubMed  Google Scholar 

  • Taketani, Y. 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. 7, 16713 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  • Weinreb, R. N., Aung, T. & Medeiros, F. A. The pathophysiology and treatment of glaucoma: a review. JAMA 311, 1901–1911 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  • Tham, Y. C. et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology 121, 2081–2090 (2014).

    Article  PubMed  Google Scholar 

  • Weinreb, R. N. & Khaw, P. T. Primary open-angle glaucoma. Lancet 363, 1711–1720 (2004).

    Article  PubMed  Google Scholar 

  • Stone, E. M. et al. Identification of a gene that causes primary open angle glaucoma. Science 275, 668–670 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Goldenstein, H., Levy, N. S. & Levy, A. P. Haptoglobin genotype and its role in determining heme-iron mediated vascular disease. Pharmacol. Res. 66, 1–6 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kasetti, R. B. et al. Autophagy stimulation reduces ocular hypertension in a murine glaucoma model via autophagic degradation of mutant myocilin. JCI Insight 6, e143359 (2021).

  • Jain, A. et al. CRISPR-Cas9-based treatment of myocilin-associated glaucoma. Proc. Natl Acad. Sci. USA 114, 11199–11204 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, J. et al. Gene therapy for glaucoma by ciliary body aquaporin 1 disruption using CRISPR-Cas9. Mol. Ther. 28, 820–829 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Derynck, R. & Budi, E. H. Specificity, versatility, and control of TGF-β family signaling. Sci. Signal. 12, eaav5183 (2019).

  • Cousins, S. W., McCabe, M. M., Danielpour, D. & Streilein, J. W. Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest. Ophthalmol. Vis. Sci. 32, 2201–2211 (1991).

    CAS  PubMed  Google Scholar 

  • Granstein, R. D. et al. Aqueous humor contains transforming growth factor-beta and a small (less than 3500 daltons) inhibitor of thymocyte proliferation. J. Immunol. 144, 3021–3027 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Jampel, H. D., Roche, N., Stark, W. J. & Roberts, A. B. Transforming growth factor-beta in human aqueous humor. Curr. Eye Res. 9, 963–969 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Ozcan, A. A., Ozdemir, N. & Canataroglu, A. The aqueous levels of TGF-beta2 in patients with glaucoma. Int. Ophthalmol. 25, 19–22 (2004).

    Article  PubMed  Google Scholar 

  • Yamamoto, N., Itonaga, K., Marunouchi, T. & Majima, K. Concentration of transforming growth factor beta2 in aqueous humor. Ophthalmic Res. 37, 29–33 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Trivedi, R. H., Nutaitis, M., Vroman, D. & Crosson, C. E. Influence of race and age on aqueous humor levels of transforming growth factor-beta 2 in glaucomatous and nonglaucomatous eyes. J. Ocul. Pharm. Ther. 27, 477–480 (2011).

    Article  CAS  Google Scholar 

  • Pena, J. D., Taylor, A. W., Ricard, C. S., Vidal, I. & Hernandez, M. R. Transforming growth factor beta isoforms in human optic nerve heads. Br. J. Ophthalmol. 83, 209–218 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rayana, N. P. et al. Using CRISPR interference as a therapeutic approach to treat TGFβ2-induced ocular hypertension and glaucoma. Invest. Ophthalmol. Vis. Sci. 62, 7 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gilbert, L. A. et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154, 442–451 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thakore, P. I. et al. Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements. Nat. Methods 12, 1143–1149 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carmeliet, P. Angiogenesis in health and disease. Nat. Med. 9, 653–660 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Wong, T. Y., Cheung, C. M., Larsen, M., Sharma, S. & Simó, R. Diabetic retinopathy. Nat. Rev. Dis. Prim. 2, 16012 (2016).

    Article  PubMed  Google Scholar 

  • Hellström, A., Smith, L. E. & Dammann, O. Retinopathy of prematurity. Lancet 382, 1445–1457 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  • Jager, R. D., Mieler, W. F. & Miller, J. W. Age-related macular degeneration. N. Engl. J. Med. 358, 2606–2617 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Guymer, R. H. & Campbell, T. G. Age-related macular degeneration. Lancet 401, P1459–P1472 (2023).

  • Campochiaro, P. A. Molecular pathogenesis of retinal and choroidal vascular diseases. Prog. Retin. Eye Res. 49, 67–81 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller, J. W., Le Couter, J., Strauss, E. C. & Ferrara, N. Vascular endothelial growth factor A in intraocular vascular disease. Ophthalmology 120, 106–114 (2013).

    Article  PubMed  Google Scholar 

  • Holmgaard, A. et al. In vivo knockout of the Vegfa gene by lentiviral delivery of CRISPR/Cas9 in mouse retinal pigment epithelium cells. Mol. Ther. Nucleic Acids 9, 89–99 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koo, T. et al. CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration. Nat. Commun. 9, 1855 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  • Ling, S. et al. Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa-targeting guide RNA prevents wet age-related macular degeneration in mice. Nat. Biomed. Eng. 5, 144–156 (2021).

    Article  CAS  PubMed  Google Scholar 

  • Kim, K. et al. Genome surgery using Cas9 ribonucleoproteins for the treatment of age-related macular degeneration. Genome Res. 27, 419–426 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung, S. H. et al. CRISPR-based VEGF suppression using paired guide RNAs for treatment of choroidal neovascularization. Mol. Ther. Nucleic Acids 28, 613–622 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mitchell, G. A. et al. An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina. J. Clin. Investig. 81, 630–633 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duncan, J. L. et al. Inherited retinal degenerations: current landscape and knowledge gaps. Transl. Vis. Sci. Technol. 7, 6 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  • Thompson, D. A. et al. Advancing clinical trials for inherited retinal diseases: recommendations from the Second Monaciano Symposium. Transl. Vis. Sci. Technol. 9, 2 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  • Georgiou, M., Fujinami, K. & Michaelides, M. Inherited retinal diseases: therapeutics, clinical trials and end points—a review. Clin. Exp. Ophthalmol. 49, 270–288 (2021).

    Article  PubMed  Google Scholar 

  • Cideciyan, A. V. et al. Measures of function and structure to determine phenotypic features, natural history, and treatment outcomes in inherited retinal diseases. Annu. Rev. Vis. Sci. 7, 747–772 (2021).

    Article  PubMed  Google Scholar 

  • Verbakel, S. K. et al. Non-syndromic retinitis pigmentosa. Prog. Retin. Eye Res. 66, 157–186 (2018).

    Article  PubMed  Google Scholar 

  • Hosseini Shabanan, S., Seyedmirzaei, H., Barnea, A., Hanaei, S. & Rezaei, N. Stem cell transplantation as a progressing treatment for retinitis pigmentosa. Cell Tissue Res. 387, 177–205 (2022).

    Article  PubMed  Google Scholar 

  • Stingl, K. et al. Subretinal visual implant Alpha IMS—clinical trial interim report. Vis. Res. 111, 149–160 (2015).

    Article  PubMed  Google Scholar 

  • Merkle, F. T. et al. Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature 545, 229–233 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petrs-Silva, H. & Linden, R. Advances in gene therapy technologies to treat retinitis pigmentosa. Clin. Ophthalmol. 8, 127–136 (2014).

    PubMed  Google Scholar 

  • Bakondi, B. et al. In vivo CRISPR/Cas9 gene editing corrects retinal dystrophy in the S334ter-3 rat model of autosomal dominant retinitis pigmentosa. Mol. Ther. 24, 556–563 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giannelli, S. G. et al. Cas9/sgRNA selective targeting of the P23H Rhodopsin mutant allele for treating retinitis pigmentosa by intravitreal AAV9.PHP.B-based delivery. Hum. Mol. Genet. 27, 761–779 (2018).

    Article  CAS  PubMed  Google Scholar 

  • Gumerson, J. D. et al. Restoration of RPGR expression in vivo using CRISPR/Cas9 gene editing. Gene Ther. 29, 81–93 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Cai, Y. et al. In vivo genome editing rescues photoreceptor degeneration via a Cas9/RecA-mediated homology-directed repair pathway. Sci. Adv. 5, eaav3335 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin, H. et al. Vision rescue via unconstrained in vivo prime editing in degenerating neural retinas. J. Exp. Med. 220, e20220776 (2023).

    Article  CAS  PubMed  Google Scholar 

  • Tanna, P., Strauss, R. W., Fujinami, K. & Michaelides, M. Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options. Br. J. Ophthalmol. 101, 25–30 (2017).

    Article  PubMed  Google Scholar 

  • Fujinami, K. et al. Clinical and molecular characteristics of childhood-onset Stargardt disease. Ophthalmology 122, 326–334 (2015).

    Article  PubMed  Google Scholar 

  • Molday, L. L., Rabin, A. R. & Molday, R. S. ABCR expression in foveal cone photoreceptors and its role in Stargardt macular dystrophy. Nat. Genet. 25, 257–258 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Allikmets, R. et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat. Genet. 15, 236–246 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Molday, R. S., Garces, F. A., Scortecci, J. F. & Molday, L. L. Structure and function of ABCA4 and its role in the visual cycle and Stargardt macular degeneration. Prog. Retin. Eye Res. 89, 101036 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Cideciyan, A. V. et al. Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence. Hum. Mol. Genet. 13, 525–534 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Beharry, S., Zhong, M. & Molday, R. S. N-retinylidene-phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor-specific ABC transporter ABCA4 (ABCR). J. Biol. Chem. 279, 53972–53979 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Quazi, F., Lenevich, S. & Molday, R. S. ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer. Nat. Commun. 3, 925 (2012).

    Article  PubMed  Google Scholar 

  • Chen, Y. et al. Mechanism of all-trans-retinal toxicity with implications for Stargardt disease and age-related macular degeneration. J. Biol. Chem. 287, 5059–5069 (2012).

    Article  CAS  PubMed  Google Scholar 

  • Weng, J. et al. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice. Cell 98, 13–23 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Grieger, J. C. & Samulski, R. J. Packaging capacity of adeno-associated virus serotypes: impact of larger genomes on infectivity and postentry steps. J. Virol. 79, 9933–9944 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zernant, J. et al. Analysis of the ABCA4 genomic locus in Stargardt disease. Hum. Mol. Genet. 23, 6797–6806 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sangermano, R. et al. ABCA4 midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease. Genome Res. 28, 100–110 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scotti, M. M. & Swanson, M. S. RNA mis-splicing in disease. Nat. Rev. Genet. 17, 19–32 (2016).

    Article  CAS  PubMed  Google Scholar 

  • Cartegni, L., Chew, S. L. & Krainer, A. R. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat. Rev. Genet. 3, 285–298 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Ong, C. T. & Corces, V. G. Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat. Rev. Genet. 12, 283–293 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Angeli, P. et al. Effective splicing restoration of a deep-intronic ABCA4 variant in cone photoreceptor precursor cells by CRISPR/SpCas9 approaches. Mol. Ther. Nucleic Acids 29, 511–524 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  • den Hollander, A. I., Roepman, R., Koenekoop, R. K. & Cremers, F. P. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog. Retin. Eye Res. 27, 391–419 (2008).

    Article  Google Scholar 

  • Kumaran, N., Moore, A. T., Weleber, R. G. & Michaelides, M. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions. Br. J. Ophthalmol. 101, 1147–1154 (2017).

    Article  PubMed  Google Scholar 

  • Bennett, J. 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. Lancet 388, 661–672 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maguire, A. M. et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials. Ophthalmology 126, 1273–1285 (2019).

    Article  PubMed  Google Scholar 

  • Rachel, R. A., Li, T. & Swaroop, A. Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins. Cilia 1, 22 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perrault, I. et al. Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. Hum. Mutat. 28, 416 (2007).

    Article  PubMed  Google Scholar 

  • Vallespin, E. et al. Frequency of CEP290 c.2991_1655A>G mutation in 175 Spanish families affected with Leber congenital amaurosis and early-onset retinitis pigmentosa. Mol. Vis. 13, 2160–2162 (2007).

    PubMed  Google Scholar 

  • den Hollander, A. I. et al. Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. Am. J. Hum. Genet. 79, 556–561 (2006).

    Article  Google Scholar 

  • Maeder, M. L. et al. Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nat. Med. 25, 229–233 (2019).

    Article  CAS  PubMed  Google Scholar 

  • Cai, X., Conley, S. M. & Naash, M. I. RPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet. 30, 57–62 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jo, D. H. et al. CRISPR-Cas9-mediated therapeutic editing of Rpe65 ameliorates the disease phenotypes in a mouse model of Leber congenital amaurosis. Sci. Adv. 5, eaax1210 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jang, H.-K. et al. High-purity production and precise editing of DNA base editing ribonucleoproteins. Sci. Adv. 7, eabg2661 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jang, H. et al. Application of prime editing to the correction of mutations and phenotypes in adult mice with liver and eye diseases. Nat. Biomed. Eng. 6, 181–194 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Reichel, F. F. et al. AAV8 can induce innate and adaptive immune response in the primate eye. Mol. Ther. 25, 2648–2660 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong, W. et al. AAV cis-regulatory sequences are correlated with ocular toxicity. Proc. Natl Acad. Sci. USA 116, 5785–5794 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bainbridge, J. W. et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N. Engl. J. Med. 358, 2231–2239 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Dimopoulos, I. S. et al. Two-year results after AAV2-mediated gene therapy for choroideremia: the Alberta experience. Am. J. Ophthalmol. 193, 130–142 (2018).

    Article  PubMed  Google Scholar 

  • Dalkara, D. et al. In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous. Sci. Transl. Med. 5, 189ra176 (2013).

    Article  Google Scholar 

  • Chan, Y. K. et al. Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses. Sci. Transl. Med. 13, eabd3438 (2021).

  • Toral, M. A. et al. Investigation of Cas9 antibodies in the human eye. Nat. Commun. 13, 1053 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chandler, R. J., Sands, M. S. & Venditti, C. P. Recombinant adeno-associated viral integration and genotoxicity: insights from animal models. Hum. Gene Ther. 28, 314–322 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donsante, A. et al. Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors. Gene Ther. 8, 1343–1346 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Finn, J. D. et al. A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing. Cell Rep. 22, 2227–2235 (2018).

    Article  CAS  PubMed  Google Scholar 

  • Lyu, P., Javidi-Parsijani, P., Atala, A. & Lu, B. Delivering Cas9/sgRNA ribonucleoprotein (RNP) by lentiviral capsid-based bionanoparticles for efficient ‘hit-and-run’ genome editing. Nucleic Acids Res. 47, e99 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  • Mangeot, P. E. et al. Genome editing in primary cells and in vivo using viral-derived nanoblades loaded with Cas9-sgRNA ribonucleoproteins. Nat. Commun. 10, 45 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banskota, S. et al. Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins. Cell 185, 250–265.e216 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel, S. R. et al. Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye. Invest. Ophthalmol. Vis. Sci. 53, 4433–4441 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olsen, T. W. et al. Drug tissue distribution of TUDCA from a biodegradable suprachoroidal implant versus intravitreal or systemic delivery in the pig model. Transl. Vis. Sci. Technol. 9, 11 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  • Muya, L., Kansara, V., Cavet, M. E. & Ciulla, T. Suprachoroidal injection of triamcinolone acetonide suspension: ocular pharmacokinetics and distribution in rabbits demonstrates high and durable levels in the chorioretina. J. Ocul. Pharm. Ther. 38, 459–467 (2022).

    CAS  Google Scholar 

  • Yeh, S. et al. Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis: phase 3 randomized trial. Ophthalmology 127, 948–955 (2020).

    Article  PubMed  Google Scholar 

  • Barakat, M. R. et al. Suprachoroidal CLS-TA plus intravitreal aflibercept for diabetic macular edema: a randomized, double-masked, parallel-design, controlled study. Ophthalmol. Retin. 5, 60–70 (2021).

    Article  Google Scholar 

  • Campochiaro, P. A. et al. Suprachoroidal triamcinolone acetonide for retinal vein occlusion: results of the tanzanite study. Ophthalmol. Retin. 2, 320–328 (2018).

    Article  Google Scholar 

  • Jung, J. H., Kim, S. S., Chung, H., Hejri, A. & Prausnitz, M. R. Six-month sustained delivery of anti-VEGF from in-situ forming hydrogel in the suprachoroidal space. J. Control Release 352, 472–484 (2022).

    Article  CAS  PubMed  Google Scholar 

  • Shen, J. et al. Suprachoroidal gene transfer with nonviral nanoparticles. Sci. Adv. 6, eaba1606 (2020).

  • Ding, K. et al. AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression. J. Clin. Invest. 129, 4901–4911 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kansara, V. S. et al. Suprachoroidally delivered DNA nanoparticles transfect retina and retinal pigment epithelium/choroid in rabbits. Transl. Vis. Sci. Technol. 9, 21 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu, D., Khan, M. A. & Ho, A. C. Creating an ocular biofactory: surgical approaches in gene therapy for acquired retinal diseases. Asia Pac. J. Ophthalmol. 10, 5–11 (2021).

    Article  CAS  Google Scholar 

  • spot_img

    Latest Intelligence

    spot_img