Genome Surgery and Gene Therapy in Retinal Disorders

Overview

Journal Yale J Biol Med

Specialty Biology

Date 2017 Dec 21

PMID 29259518

Citations 5

Authors

Lawrence Chan

Vinit B Mahajan

Stephen H Tsang

Affiliations

Soon will be listed here.

Abstract

The emergence of genome surgery techniques like the clustered regularly interspaced short palindromic repeats (CRISPR) editing technology has given researchers a powerful tool for precisely introducing targeted changes within the genome. New modifications to the CRISPR-Cas system have been made since its recent discovery, such as high-fidelity Cas9 variants to reduce off-target effects and transcriptional activation/silencing with CRISPRa/CRISPRi. The applications of CRISPR-Cas and gene therapy in ophthalmic diseases have been necessary and fruitful, especially given the impact of blinding diseases on society and the large number of monogenic disorders of the eye. This review discusses the impact that CRISPR-Cas has had on furthering our understanding of disease mechanisms and potential therapies for inherited eye diseases. Furthermore, we explore a brief overview of recent and ongoing gene therapy clinical trials in retinal diseases, and conclude with the implications of genome surgery on the outlook of future therapeutic interventions.

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References

Mojica F, Diez-Villasenor C, Garcia-Martinez J, Almendros C . Short motif sequences determine the targets of the prokaryotic CRISPR defence system. Microbiology (Reading). 2009; 155(Pt 3):733-740. DOI: 10.1099/mic.0.023960-0. View

Pittler S, KEELER C, Sidman R, Baehr W . PCR analysis of DNA from 70-year-old sections of rodless retina demonstrates identity with the mouse rd defect. Proc Natl Acad Sci U S A. 1993; 90(20):9616-9. PMC: 47620. DOI: 10.1073/pnas.90.20.9616. View

Redmond T . Focus on Molecules: RPE65, the visual cycle retinol isomerase. Exp Eye Res. 2008; 88(5):846-7. PMC: 2692084. DOI: 10.1016/j.exer.2008.07.015. View

Scholze H, Boch J . TAL effectors are remote controls for gene activation. Curr Opin Microbiol. 2011; 14(1):47-53. DOI: 10.1016/j.mib.2010.12.001. View

Yu J, Vodyanik M, Smuga-Otto K, Antosiewicz-Bourget J, Frane J, Tian S . Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007; 318(5858):1917-20. DOI: 10.1126/science.1151526. View

Charbel Issa P, Barnard A, Herrmann P, Washington I, MacLaren R . Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization. Proc Natl Acad Sci U S A. 2015; 112(27):8415-20. PMC: 4500285. DOI: 10.1073/pnas.1506960112. View

Zhong H, Chen Y, Li Y, Chen R, Mardon G . CRISPR-engineered mosaicism rapidly reveals that loss of Kcnj13 function in mice mimics human disease phenotypes. Sci Rep. 2015; 5:8366. PMC: 4322368. DOI: 10.1038/srep08366. View

Cideciyan A, Jacobson S, Beltran W, Sumaroka A, Swider M, Iwabe S . Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci U S A. 2013; 110(6):E517-25. PMC: 3568385. DOI: 10.1073/pnas.1218933110. View

Forsythe J, Jiang B, Iyer N, Agani F, Leung S, Koos R . Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996; 16(9):4604-13. PMC: 231459. DOI: 10.1128/MCB.16.9.4604. View

10.

Barrangou R, Doudna J . Applications of CRISPR technologies in research and beyond. Nat Biotechnol. 2016; 34(9):933-941. DOI: 10.1038/nbt.3659. View

11.

Alexandru M, Alexandra N . Wet age related macular degeneration management and follow-up. Rom J Ophthalmol. 2016; 60(1):9-13. PMC: 5712923. View

12.

Wu W, Tsai Y, Justus S, Lee T, Zhang L, Lin C . CRISPR Repair Reveals Causative Mutation in a Preclinical Model of Retinitis Pigmentosa. Mol Ther. 2016; 24(8):1388-94. PMC: 5023380. DOI: 10.1038/mt.2016.107. View

13.

Kleinstiver B, Pattanayak V, Prew M, Tsai S, Nguyen N, Zheng Z . High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016; 529(7587):490-5. PMC: 4851738. DOI: 10.1038/nature16526. View

14.

Weil D, Kussel P, Blanchard S, Levy G, Levi-Acobas F, Drira M . The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Nat Genet. 1997; 16(2):191-3. DOI: 10.1038/ng0697-191. View

15.

Cideciyan A, Hauswirth W, Aleman T, Kaushal S, Schwartz S, Boye S . Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Hum Gene Ther. 2009; 20(9):999-1004. PMC: 2829287. DOI: 10.1089/hum.2009.086. View

16.

Konermann S, Brigham M, Trevino A, Joung J, Abudayyeh O, Barcena C . Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature. 2014; 517(7536):583-8. PMC: 4420636. DOI: 10.1038/nature14136. View

17.

Bogomazova A, Lagarkova M, Tskhovrebova L, Shutova M, Kiselev S . Error-prone nonhomologous end joining repair operates in human pluripotent stem cells during late G2. Aging (Albany NY). 2011; 3(6):584-96. PMC: 3164367. DOI: 10.18632/aging.100336. View

18.

Hauswirth W, Aleman T, Kaushal S, Cideciyan A, Schwartz S, Wang L . Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther. 2008; 19(10):979-90. PMC: 2940541. DOI: 10.1089/hum.2008.107. View

19.

Bassuk A, Zheng A, Li Y, Tsang S, Mahajan V . Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells. Sci Rep. 2016; 6:19969. PMC: 4728485. DOI: 10.1038/srep19969. View

20.

Hirsch M, Wolf S, Samulski R . Delivering Transgenic DNA Exceeding the Carrying Capacity of AAV Vectors. Methods Mol Biol. 2015; 1382:21-39. PMC: 4971574. DOI: 10.1007/978-1-4939-3271-9_2. View