Generation of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology

Dabrowska, Magdalena; Ciolak, Agata; Kozlowska, Emilia; Fiszer, Agnieszka; Olejniczak, Marta

doi:10.3390/ijms21051854

Open AccessArticle

Generation of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology

by

Magdalena Dabrowska

¹,

Agata Ciolak

²

,

Emilia Kozlowska

²

,

Agnieszka Fiszer

²

and

Marta Olejniczak

^1,*

¹

Department of Genome Engineering, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

²

Department of Medical Biotechnology, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(5), 1854; https://doi.org/10.3390/ijms21051854

Submission received: 8 January 2020 / Revised: 17 February 2020 / Accepted: 5 March 2020 / Published: 8 March 2020

(This article belongs to the Special Issue Genome Editing Therapies)

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Abstract

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by the expansion of CAG repeats in exon 1 of the huntingtin gene (HTT). Despite its monogenic nature, HD pathogenesis is still not fully understood, and no effective therapy is available to patients. The development of new techniques such as genome engineering has generated new opportunities in the field of disease modeling and enabled the generation of isogenic models with the same genetic background. These models are very valuable for studying the pathogenesis of a disease and for drug screening. Here, we report the generation of a series of homozygous HEK 293T cell lines with different numbers of CAG repeats at the HTT locus and demonstrate their usefulness for testing therapeutic reagents. In addition, using the CRISPR-Cas9 system, we corrected the mutation in HD human induced pluripotent stem cells and generated a knock-out of the HTT gene, thus providing a comprehensive set of isogenic cell lines for HD investigation.

Keywords: genome editing; iPSCs; aberrant splicing; CAG repeats; Huntington’s disease; CRISPR

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MDPI and ACS Style

Dabrowska, M.; Ciolak, A.; Kozlowska, E.; Fiszer, A.; Olejniczak, M. Generation of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology. Int. J. Mol. Sci. 2020, 21, 1854. https://doi.org/10.3390/ijms21051854

AMA Style

Dabrowska M, Ciolak A, Kozlowska E, Fiszer A, Olejniczak M. Generation of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology. International Journal of Molecular Sciences. 2020; 21(5):1854. https://doi.org/10.3390/ijms21051854

Chicago/Turabian Style

Dabrowska, Magdalena, Agata Ciolak, Emilia Kozlowska, Agnieszka Fiszer, and Marta Olejniczak. 2020. "Generation of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology" International Journal of Molecular Sciences 21, no. 5: 1854. https://doi.org/10.3390/ijms21051854

APA Style

Dabrowska, M., Ciolak, A., Kozlowska, E., Fiszer, A., & Olejniczak, M. (2020). Generation of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology. International Journal of Molecular Sciences, 21(5), 1854. https://doi.org/10.3390/ijms21051854

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Generation of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology

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