Duane Retraction Syndrome (DRS) is characterized by limited eye movement. One of its causes is a mutation in the CHN1, MAFB, or SALL4 gene. Nowadays, the treatment for DRS is limited to glasses, occlusion, and surgery. However, this treatment has not been able to cure the disease’s hereditary issue. Another strategy to be considered for the treatment is CRISPR/Cas9, a tool for performing gene editing with a wide range of applications, including treating genetic diseases. We made sgRNA as a first step in using CRISPR/Cas9 as a treatment for DRS in silico using the CCTop website. By computing sgRNA, conducting tests, and analyzing the results, CRISPR/Cas9 may repair genetic mutations. Currently, there are no reports on the use of CRISPR/Cas9 in DRS. Hence, this study would be very useful as a starting point for using CRISPR/Cas9 as a DRS treatment. However, it needs to be further proven through in vivo, in vitro, and clinical trials study.


Al-Baradie, R., Yamada, K., St. Hilaire, C., Chan, W. M., Andrews, C., McIntosh, N., Nakano, M., Martonyi, E. J., Raymond, W. R., Okumura, S., Okihiro, M. M., & Engle, E. C. (2002). Duane Radial Ray Syndrome (Okihiro Syndrome) Maps to 20q13 and Results from Mutations in SALL4, a New Member of the SAL Family. The American Journal of Human Genetics, 71(5), 1195–1199. https://doi.org/10.1086/343821

Appukuttan, B., Gillanders, E., Juo, S.-H., Freas-Lutz, D., Ott, S., Sood, R., Van Auken, A., Bailey-Wilson, J., Wang, X., Patel, R. J., Robbins, C. M., Chung, M., Annett, G., Weinberg, K., Borchert, M. S., Trent, J. M., Brownstein, M. J., & Stout, J. T. (1999). Localization of a Gene for Duane Retraction Syndrome to Chromosome 2q31. American Journal of Human Genetics, 65(6), 1639. https://doi.org/10.1086/302656

Babar, U. (2017). Monogenic Disorders: an Overview. International Journal of Advanced Research, 5(2), 1398–1424. https://doi.org/10.21474/ijar01/3294

Bachman, J. W. (n.d.). Genetic Disorders. Taylor’s Diagnostic and Therapeutic Challenges, 35–53. https://doi.org/10.1007/0-387-27287-9_3

Barbe, M. E., Scott, W. E., & Kutschke, P. J. (2004). A simplified approach to the treatment of Duane’s syndrome. British Journal of Ophthalmology, 88(1), 131–138. https://doi.org/10.1136/BJO.88.1.131

Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D. A., & Horvath, P. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science, 315(5819), 1709–1712. https://doi.org/10.1126/science.1138140

Barry, B. J., Whitman, M. C., Hunter, D. G., & Engle, E. C. (2019). Duane Syndrome. Ocular Disease: Mechanisms and Management, 438–444. https://www.ncbi.nlm.nih.gov/books/NBK1190/

Bhaya, D., Davison, M., & Barrangou, R. (2011). CRISPR-cas systems in bacteria and archaea: Versatile small RNAs for adaptive defense and regulation. Annual Review of Genetics, 45, 273–297. https://doi.org/10.1146/annurev-genet-110410-132430

Biler, E. D., Ilim, O., Onay, H., & Uretmen, O. (2017). CHN1 gene mutation analysis in patients with Duane retraction syndrome. Journal of AAPOS, 21(6), 472-475.e2. https://doi.org/10.1016/J.JAAPOS.2017.07.208

Bradford, J., & Perrin, D. (2019). A benchmark of computational CRISPR-Cas9 guide design methods. PLOS Computational Biology, 15(8), e1007274. https://doi.org/10.1371/JOURNAL.PCBI.1007274

Carroll, D. (2017). Focus: Genome Editing: Genome Editing: Past, Present, and Future. The Yale Journal of Biology and Medicine, 90(4), 653. /pmc/articles/PMC5733845/

Duane, A. (1996). Congenital Deficiency of Abduction, Associated With Impairment of Adduction, Retraction Movements, Contraction of the Palpebral Fissure and Oblique Movements of the Eye. Archives of Ophthalmology, 114(10), 1255. https://doi.org/10.1001/archopht.1996.01100140455017

Hana, S., Peterson, M., McLaughlin, H, Marshall, E., Fabian, A. J, ………. Lo, S.H. (2021). Highly efficient neuronal gene knockout in vivo by CRISPR-Cas9 via neonatal intracerebroventricular injection of AAV in mice. Gene Ther, 28, 646–658. https://doi.org/10.1038/s41434-021-00224-2

Gaur, N., & Sharma, P. (2019). Management of Duane retraction syndrome: A simplified approach. Indian Journal of Ophthalmology, 67(1), 16. https://doi.org/10.4103/IJO.IJO_967_18

Gupta, R. M., & Musunuru, K. (2014). Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. The Journal of Clinical Investigation, 124(10), 4154. https://doi.org/10.1172/JCI72992

Han, W., & She, Q. (2017). CRISPR History: Discovery, Characterization, and Prosperity. Progress in Molecular Biology and Translational Science (Vol. 152, pp. 1–21). Elsevier B.V. https://doi.org/10.1016/bs.pmbts.2017.10.001

Hanna, R. E., & Doench, J. G. (2020). Design and analysis of CRISPR–Cas experiments. Nature Biotechnology, 38(7), 813–823. https://doi.org/10.1038/S41587-020-0490-7

Hsu, P. D., Lander, E. S., & Zhang, F. (2014). Development and applications of CRISPR-Cas9 for genome engineering. In Cell (Vol. 157, Issue 6, pp. 1262–1278). Elsevier B.V. https://doi.org/10.1016/j.cell.2014.05.010

Huber, A. (1974). Electrophysiology of the retraction syndromes. The British Journal of Ophthalmology, 58(3), 293. https://doi.org/10.1136/BJO.58.3.293

Hunter, D. J. (2005). Gene–environment interactions in human diseases. Nature Reviews Genetics, 6(4), 287–298. https://doi.org/10.1038/nrg1578

Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., & Nakatura, A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isoenzyme conversion in Escherichia coli, and identification of the gene product. Journal of Bacteriology, 169(12), 5429–5433. https://doi.org/10.1128/jb.169.12.5429-5433.1987

Jackson, M., Marks, L., May, G., & Wilson, J. B. (2018). The genetic basis of disease. Essays in Biochemistry, 62(5), 643–723. https://doi.org/10.1042/EBC20170053

Jansen, R., Van Embden, J. D. A., Gaastra, W., & Schouls, L. M. (2002). Identification of genes that are associated with DNA repeats in prokaryotes. Molecular Microbiology, 43(6), 1565–1575. https://doi.org/10.1046/j.1365-2958.2002.02839.x

Kalevar, A., Ong Tone, S., & Flanders, M. (2015). Duane syndrome: Clinical features and surgical management. Canadian Journal of Ophthalmology, 50(4), 310–313. https://doi.org/10.1016/J.JCJO.2015.05.005

Kekunnaya, R., & Negalur, M. (2017). Duane retraction syndrome: causes, effects and management strategies. Clinical Ophthalmology, 11, 1917–1930. https://doi.org/10.2147/OPTH.S127481

Kotagama, O. W., Jayasinghe, C. D., & Abeysinghe, T. (2019). Era of genomic medicine: A narrative review on CRISPR technology as a potential therapeutic tool for human diseases. BioMed Research International, 2019. https://doi.org/10.1155/2019/1369682

Labuhn, M., Adams, F. F., Ng, M., Knoess, S., Schambach, A., Charpentier, E. M., Schwarzer, A., Mateo, J. L., Klusmann, J.-H., & Heckl, D. (2018). Refined sgRNA efficacy prediction improves large- and small-scale CRISPR–Cas9 applications. Nucleic Acids Research, 46(3), 1375–1385. https://doi.org/10.1093/NAR/GKX1268

Lattanzi, A., Camarena, J., Lahiri, P., Segal, H., Srifa, W., Vakulskas, C. A., Frock, R. L., Kenrick, J., Lee, C., Talbott, N., Skowronski, J., Cromer, M. K., Charlesworth, C. T., Bak, R. O., Mantri, S., Bao, G., DiGiusto, D., Tisdale, J., Wright, J. F., … Porteus, M. H. (2021). Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease. Science Translational Medicine, 13(598), eabf2444. https://doi.org/10.1126/SCITRANSLMED.ABF2444

Leenay, R. T., & Beisel, C. L. (2017). Deciphering, communicating, and engineering the CRISPR PAM. Journal of Molecular Biology, 429(2), 177. https://doi.org/10.1016/J.JMB.2016.11.024

Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018). Delivering CRISPR: a review of the challenges and approaches. Drug Delivery, 25(1), 1234. https://doi.org/10.1080/10717544.2018.1474964

Liu, G., Zhang, Y., & Zhang, T. (2020). Computational approaches for effective CRISPR guide RNA design and evaluation. Computational and Structural Biotechnology Journal, 18, 35–44. https://doi.org/10.1016/J.CSBJ.2019.11.006

Miyake, N., Chilton, J., Psatha, M., Cheng, L., Andrews, C., Chan, W.-M., Law, K., Crosier, M., Lindsay, S., Cheung, M., Allen, J., Gutowski, N. J., Ellard, S., Young, E., Iannaccone, A., Appukuttan, B., Stout, J. T., Christiansen, S., Ciccarelli, M. L., … Engle, E. C. (2008). Human CHN1 mutations hyperactivate α2-chimaerin and cause Duane’s retraction syndrome. Science (New York, N.Y.), 321(5890), 839. https://doi.org/10.1126/SCIENCE.1156121

Mohr, S. E., Hu, Y., Ewen-Campen, B., Housden, B. E., Viswanatha, R., & Perrimon, N. (2016). CRISPR guide RNA design for research applications. The FEBS Journal, 283(17), 3232–3238. https://doi.org/10.1111/FEBS.13777

Mojica, F. J. M., & Rodriguez-Valera, F. (2016). The discovery of CRISPR in archaea and bacteria. FEBS Journal, 283(17), 3162-9. https://doi.org/10.1111/febs.13766

Musunuru, K. (2017). Genome editing: The recent history and perspective in cardiovascular diseases. Journal of the American College of Cardiology, 70(22), 2808. https://doi.org/10.1016/J.JACC.2017.10.002

Redman, M., King, A., Watson, C., & King, D. (2016). What is CRISPR/Cas9? 101, 213–215. https://doi.org/10.1136/archdischild-2016-310459

Schliesser, J. A., Sprunger, D. T., & Helveston, E. M. (2016). Type 4 duane syndrome. Journal of AAPOS, 20(4), 301–304. https://doi.org/10.1016/J.JAAPOS.2016.05.012

Stemmer, M., Thumberger, T., Keyer, M. del S., Wittbrodt, J., & Mateo, J. L. (2015). CCTop: An intuitive, flexible and reliable CRISPR/Cas9 target prediction tool. PLOS ONE, 10(4), e0124633. https://doi.org/10.1371/JOURNAL.PONE.0124633

Theisen, A., & Shaffer, L. G. (2010). Disorders caused by chromosome abnormalities. The Application of Clinical Genetics, 3, 159. https://doi.org/10.2147/TACG.S8884



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.