A genome editing technology and capabilities of its application in cellular neurobiology

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Abstract

A number of fundamental breakthroughs in cellular and molecular biology provided the basis for several modern sophisticated approaches to modeling of human neurological (primarily neurodegenerative) diseases. In particular, targeted genome editing by artificial nuclease systems (CRISPR/CAS9, etc.) enables a highly specific correction of genetic defects at the cellular level. An especially promising area is application of the genome editing technology in specialized neurons and induced pluripotent stem cells (iPSCs) derived from fibroblasts of patients with inherited forms of neurodegeneration by cell reprogramming. The article provides a brief analysis of programmable nuclease systems and describes mechanisms of their activity as well as advantages, disadvantages, and capabilities of their applications in modeling and correction of neurodegenerative diseases. The authors generalize their own experience in cellular modeling of the PARK2 type of Parkinson’s disease on the culture of dopaminergic neurons differentiated from iPSCs. The article provides preliminary data related to the capability of editing the cellular genome at mutant sites PARK2.

About the authors

A. S. Vetchinova

Research Center of Neurology, Moscow

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

E. V. Konovalova

Research Center of Neurology, Moscow

Email: platonova@neurology.ru
Russian Federation

E. A. Lunev

I. Kant Baltic Federal University, Kaliningrad

Email: platonova@neurology.ru
Russian Federation

S. N. Illarioshkin

Research Center of Neurology, Moscow

Email: platonova@neurology.ru
Russian Federation

References

  1. Богомазова А.Н., Васина Е.М., Киселев С.Л. и др. Генетическое репрограммирование клеток: новая технология для фундаментальных исследований и практического использования. Генетика. 2015; 4: 466–478.
  2. Васильева Е.А., Мелино Д., Барлев Н.А. Применение системы направленного геномного редактирования CRISPR/Cas к плюрипотентным стволовым клеткам. Цитология. 2015; 1: 19–30.
  3. Завалишин И.А., Яхно Н.Н., Гаврилова С.И. (ред.) Нейродегенеративные болезни и старение. М.: А.А.А., 2001.
  4. Загоровская Т.Б., Иллариошкин С.Н., Сломинский П.А. и др. Клинико-генетический анализ ювенильного паркинсонизма в России. Журн. неврологии и психиатрии им. С.С. Корсакова. 2004; 8: 66–72.
  5. Иллариошкин С.Н., Загоровская И.А., Иванова-Смоленская И.А.,Маркова Е.Д. Генетические аспекты болезни Паркинсона. Неврол. журн. 2002; 5: 47–51.
  6. Иллариошкин С.Н., Иванова-Смоленская И.А., Маркова Е.Д. Новый механизм мутации у человека: экспансия тринуклеотидных повторов. Генетика. 1995; 31: 1478–1489.
  7. Коновалова Е.В., Лопачева О.М., Гривенников И.А. и др. Экспрессия про- и антиапоптотических факторов в индуцированных плюрипотентных стволовых клетках здорового донора и пациента с болезнью Паркинсона, являющегося носителем мутаций в гене PARK2. Acta Naturae. 2015; 7 (4).
  8. Коновалова Е.В., Новосадова Е.В., Гривенников И.А., Иллариош-кин С.Н. Фенотипические различия культур нейронов, получаемых путем репрограммирования фибробластов пациентов с мутациями в генах паркинсонизма LRRK2 и PARK2. Бюлл. эксперим. биол. мед. 2015; 6: 749–753.
  9. Лебедева О.С., Лагарькова М.А., Иллариошкин С.Н. и др. Индуцированные плюрипотентные стволовые клетки: новые возможности в нейробиологии и нейротрансплантологии. Анн. клин. и эксперим. неврол. 2011; 4: 37–45.
  10. Лысогорская Е.В., Абрамычева Н.Ю., Захарова М.Н., Иллариошкин С.Н. Частота мутаций в гене SOD1 у российских пациентов с боковым амиотрофическим склерозом. Мед. генетика 2013; 4: 32–37.
  11. Медведев С.П., Шевченко А.И., Сухих Г.Т., Закиян С.М. Индуцированные плюрипотентные стволовые клетки. Новосибирск: Изд. Сибирского отделения РАН, 2014.
  12. Немудрый А.А., Валетдинова К.Р., Медведев С.П., Закиян С.М. Системы редактирования генома TALEN и CRISPR/Cas – инструменты открытий. Acta Naturae. 2014; 23: 20–42.
  13. Barrangou R., Fremaux C., Deveau H. et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007; 315: 1709–1712.
  14. Brookmeyer R., Johnson E., Ziegler-Graham K., Arrighi M.H. Forecasting the global burden of Alzheimer’s disease. Alzheimer’s and Dementia. 2007; 3: 186–191.
  15. Chapdelaine P., Coulombe Z., Chikh A. et al. A potential new therapeutic approach for Friedreich ataxia: induction of frataxin expression with TALE proteins. Mol. Ther. Nucleic Acids. 2013; 2 (9): e119.
  16. Chen K., Gao C.J. TALENs: customizable molecular DNA scissors for genome engineering of plants. Genet. Genomics. 2013; 40: 271–279.
  17. Cong L., Ran F.A., Cox D. et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013; 339 (6121): 819–823.
  18. Fonfara I., Le Rhun A., Chylinski K. et al. Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems. Nucl. Acids Res. 2014; 42: 2577–2590.
  19. Gaj T., Gersbach C., Barbas C. ZNF, TALEN and CRISPR/CASbased methods for genome engineering. Trends Biotechnol. 2013; 31: 397–405.
  20. Garriga-Canut M., Agustin-Pavon C., Herrmann F. et al. Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 mice. PNAS 2012; 109: 3136–3145.
  21. Guo J.L., Lee V.M.Y. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat. Med. 2014; 20: 130–138.
  22. Hargus G, Ehrlich M., Hallmann A.-L., Kuhlmann T. Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development. Acta Neuropathol. 2014; 127: 151–173.
  23. Hunsberger J.G., Efthymiou A.G., Malik N., Behl M. Induced pluripotent stem cell models to enable in vitro models for screening in the CNS. Stem Cells Devel. 2015; 24: 1852–1864.
  24. Ingre C., Roos P.M., Piehl F. et al. Risk factors for amyotrophic lateral sclerosis. Clin Epidemiol. 2015; 7: 181–193.
  25. Jenner P., Morris H.R., Robbins T.W. et al. Parkinson’s disease – the debate on the clinical phenomenology, aetiology, pathology and pathogenesis. J. Parkinsons Dis. 2013; 3: 1–11.
  26. Kiskinis E., Sandoe J., Williams L. et al. Pathways disrupted in human ALS motor neurons indentified through genetic correction of mutant SOD1. Cell Stem Cell. 2014; 14: 781-795.
  27. Lieber M.R. The mechanism of double-strand DNA break repair bythe nonhomologous DNA end-joining pathway. Annu. Rev. Biochem. 2010; 79: 181–211.
  28. Mali P., Yang L., Esvelt K.M. et al. RNA-guided human genome engineering via Cas9. Science. 2012; 339: 823-826.
  29. Mojica F.J., Díez-Villaseñor C., García-Martínez J., Soria E. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J. Mol. Evol. 2005; 60: 174–182.
  30. Moynahan M.E., Jasin M. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat. Rev. Mol. Cell Biol. 2010; 11: 196–207.
  31. Periquet M., Lücking C.B., Vaughan J.R. et al. Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from founder effects. Am. J. Hum. Genet. 2001; 68: 617–626.
  32. Schmid-Burgk J.L., Schmidt T., Kaiser V. et al. A ligation-independent cloning technique for high-throughput assembly of transcription activator–like effector genes. Nat. Biotechnol. 2013; 31: 76–81.
  33. Singleton A.B., Farrer M.J., Bonifati V. The genetics of Parkinson’s disease: progress and therapeutic implications. Mov. Disord. 2013; 28: 14–23.
  34. Soldner F., Laganiere J., Cheng A. et al. Generation of isogenic pluripotent stem cells differing exclusively at two early-onset Parkinson point mutations. Cell. 2011; 146: 318–331.
  35. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126: 663–676.
  36. Urnov F.D., Rebar E.J., Holmes M.C. et al. Genome editing with engineered zinc finger nucleases. Nat. Rev. Genet. 2010; 11: 636–646.
  37. Wiedenheft B., Sternberg S.H., Doudna J.A. RNA-guided genetic silencing systems in bacteria and archaea. Nature. 2012; 482: 331–338.
  38. Wirdefeldt K., Adami H.O., Cole P., Trichopoulos D., Mandel J. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur. J. Epidemiol. 2011; 26 (Suppl. 1): S1–58.

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Copyright (c) 2017 Vetchinova A.S., Konovalova E.V., Lunev E.A., Illarioshkin S.N.

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