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Toward In Vivo Gene Therapy Using CRISPR

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CRISPR Gene Editing

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1961))

Abstract

CRISPR, a revolutionizing technology allowing researchers to navigate in and edit the genome, is moving on the fast track toward clinical use for ex vivo correction of disease-causing mutations in stem cells. As we await the first trials utilizing ex vivo CRISPR editing, implementation of CRISPR-based gene editing as an in vivo treatment directly in patients still remains an ultimate challenge. However, quickly accumulating evidence has provided proof-of-concept for efficacious editing in vivo. Attempts to edit genes directly in animals have largely relied on classical vector systems based on virus-based delivery of gene cassettes encoding the Cas9 endonuclease and single guide RNA, the key components of the CRISPR system. However, whereas persistent gene expression has been the primary goal of gene therapy for decades, things may be different in the case of CRISPR delivery. Is short-term presence of the CRISPR components perhaps sufficient for efficacy and ideal for safety?—and are strategies needed for restricting immune recognition of the bacteria-derived editing tool? Here, while answers to these questions still blow in the wind, we review prominent examples of genome editing with focus on targeting of genes with CRISPR in liver, muscles, and eyes of the mouse.

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Acknowledgments

Research focusing on genome engineering technologies in the laboratory of JGM is made possible through support of the Danish Council for Independent Research │ Medical Sciences (grant DFF-4004-00220), The Lundbeck Foundation (grant R126-2012-12456), the Novo Nordisk Foundation, the Hørslev Foundation, Aase og Ejnar Danielsens Fond, Grosserer L. F. Foghts Fond, Agnes og Poul Friis Fond, Oda og Hans Svenningsens Fond, Ellen og Mogens Wedell-Wedellsborgs Fond, Einar Willumsens Mindelegat, Snedkermester Sophus Jacobsen & Hustru Astrid Jacobsens Fond, Familien Hede Nielsens Fond, Carl og Ellen Hertz’ legat til læge- og naturvidenskaben, Harboefonden, Arvid Nilssons Fond, Fonden af 1870, Emil C. Hertz og hustru Inger Hertz’s Fond, Holger Hjortenberg og Hustru Dagmar Hjortenbergs Fond, Krista og Viggo Petersens Fond, Frode V. Nyegaard og Hustrus Fond, and Andersen-Isted Fonden.

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  1. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Kristian Alsbjerg Skipper & Jacob Giehm Mikkelsen

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  1. Kristian Alsbjerg Skipper
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  2. Jacob Giehm Mikkelsen
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Correspondence to Jacob Giehm Mikkelsen .

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  1. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Yonglun Luo

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Skipper, K.A., Mikkelsen, J.G. (2019). Toward In Vivo Gene Therapy Using CRISPR. In: Luo, Y. (eds) CRISPR Gene Editing. Methods in Molecular Biology, vol 1961. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9170-9_18

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  • DOI: https://doi.org/10.1007/978-1-4939-9170-9_18

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