Somatic cells reprogramming and genome editing for stargardt disease modeling for investigation and treatment


Cite item

Full Text

Abstract

Degeneration of the retina occurs both in relation to age, and as a consequence of hereditary pathologies. A clinically similar pattern is often associated with different molecular pathways and gene mutations. The arsenal of therapeutic approaches for these patients is very limited. Modern advances in cellular reprogramming and genome editing make it possible to establish a model for the disease investigation and treatment. In this study we established induced pluripotent stem cells (iPSCs) from patients with a clinical diagnosis of Stargardt>s disease. Mutation in the peripherin 2 gene was found and it was shown that the mutation does not affect the efficiency of differentiation in the pigment epithelium of the retina. Using the CRISPR/Cas9 system the mutation was corrected in the patient's iPSCs. As a result, isogeneic iPSC lines with a corrected mutation have been generated for establishing of an in vitro model of the disease and potentially suitable for personalized therapy of Stargardt disease.

Full Text

Restricted Access

About the authors

M. Y Lebedin

N.I. Vavilov Institute of General Genetics

K. S Mayorova

N.I. Vavilov Institute of General Genetics

V. V Maximov

Research Center “Kurchatov Institute"

A. N Bogomazova

N.I. Vavilov Institute of General Genetics

M. A Lagarkova

N.I. Vavilov Institute of General Genetics

S. L Kiselev

N.I. Vavilov Institute of General Genetics

Email: kiselev@vigg.ru

References

  1. Allikmets R., Singh N., Sun H. et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat. Genet. 1997; 15(3): 236-46.
  2. Nishiguchi K.M., Sandberg M.A., Gorji N. et al. Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. Hum.Mutat. 2005; 25(3): 248-58.
  3. Zhang K., Kniazeva M., Han M. et al. A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Nat. Genet. 2001; 27(1): 89-93.
  4. Edwards A.O., Donoso L.A., Ritter R. 3rd. A novel gene for autosomal dominant Stargardt-like macular dystrophy with homology to the SUR4 protein family. Invest.Ophthalmol. Vis. Sci. 2001; 42(11): 2652-63.
  5. Yang Z., Chen Y., Lillo C. et al. Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice. J.Clin. Invest. 2008; 118(8): 2908-16.
  6. Stuck M.W., Conley S.M., Naash M.I. RDS Functional Domains and Dysfunction in Disease. Adv. Exp. Med. Biol. 2016;854:217-22.
  7. Connell G.J., Molday R.S. Molecular cloning, primary structure, and orientation of the vertebrate photoreceptor cell protein peripherin in the rod outer segment disk membrane. Biochemistry 1990; 29(19):4691-8.
  8. Stuck M.W., Conley S.M., Naash M.J. Retinal Degeneration Slow (RDS) Glycosylation Plays a Role in Cone Function and in the Regulation of RDS^ROM-1 Protein Complex Formation. J. Biol. Chem. 2015; 290(46):27901-13.
  9. Schwartz S.D., Tan G., Hosseini H. et al. Subretinal transplantation of embryonic stem cell-derived retinal pigment epithelium for the treatment of macular degeneration: an assessment at 4 Years. Invest.Ophthalmol. Vis. Sci. 2016;57(5):1-9.
  10. Mandai M., Watanabe A., Kurimoto Y. et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 2017;376(11):1038-46.
  11. Честков И.В., Васильева Е.А., Иллариошкин С.Н. и др. Система для изучения бокового амиотрофического склероза на основе пациент-специфичных индуцированных плюрипотентных стволовых клеток ActaNaturae 2014; 6(1): 58-65.
  12. Лагарькова М.А., Шилов A.P, Губанова Н.И. и др. Гистогенез эмбриональных стволовых клеток человека invitro в компоненты сетчатки глаза. Клеточные технологии в биологии и медицине 2011; 4: 203-6.
  13. Shutova M.V., Surdina A.V., Ischenko D.S. et al. Anintegrati veanalysisofreprogramminginhuman isogenic system identified a clone selection criterion. Cell Cycle 2016;15(7):986-97.
  14. Eiraku M., Takata N., Ishibashi H. et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 2011; 472(7341): 51-6.
  15. Vora S., Tuttle M., Cheng J. et al. Next stop for the CRISPR revolution: RNA-guided epigenetic regulators. FEBS J. 2016; 283(17):3181-93.
  16. Cowan P.J. The use of CRISPR/Cas associated technologies for cell transplant applications. Curr.Opin. Organ Transplant. 2016; 5:461-6.
  17. Xie F., Ye L., Chang J.C.et al. Seamless gene correction of ß-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac. Genome Res. 2014;24(9):1526-33.
  18. Nakazawa M., Naoi N., Wada Y.et al. Autosomal dominant cone-rod dystrophy associated with a Val200Glu mutation of the peripherin/RDS gene. Retina 1996; 16(5): 405-10.
  19. vanSoest S., Westerveld A., de Jong P.T. et al. Retinitis pigmentosa: defined from a molecular point of view. Surv.Ophthalmol. 1999; 43(4): 321-34.
  20. Максимов В.В., Лагарькова М.А., Киселев С.Л. Генная и клеточная терапия заболеваний сетчатки глаза. Клеточная трансплантология и тканевая инженерия 2012, 7(3):12-20.
  21. Богомазова А.Н., Васина Е.М., Киселев С.Л.и др. Генетическое репрограммирование клеток: новая технология для фундаментальных исследований и практического использования. Генетика 2015;51(4): 466-78.
  22. Singh R., Shen W., Kuai D. et al. iPS cell modeling of Bestdisease: insights into the pathophysiology of an inherited macular degeneration. Hum. Mol. Genet. 2013;22(3):593-607.
  23. Singh R., Kuai D., Guziewicz K.E.et al. Pharmacological modulation of photoreceptor outer segment degradation in a human iPS cell model of inherited macular degeneration. Mol. Ther. 2015;23(11):1700-11.
  24. Bezprozvanny I., Kiselev S.L. Neurons from skin mimic brain holes. Oncotarget 2017;8(6):8997-8.
  25. Nekrasov E.D., Vigont V.A., Klyushnikov S.A.et al. Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons. Mol.Neurodegener. 2016;11(1):27-32.
  26. Shi Y., Inoue H., Wu J.C.et al.Induced pluripotent stem cell technology: a decade of progress. Nat. Rev. Drug Discov. 2017;16(2):115-30.
  27. Gasiunas G., Barrangou R., Horvath P. et al. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc. Natl. Acad. Sci.2012; 109:2579-86.
  28. Cabral T., DiCarlo J.E., Justus S.et al. CRISPR applications in ophthalmologic genome surgery. Curr.Opin.Ophthalmol. 2017;28(3):252-9.

Copyright (c) 2017 PJSC Human Stem Cells Institute


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 57156 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies