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Cellular Engineering and Disease Modeling with Gene-Editing Nucleases

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Genome Editing

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB))

Abstract

Two rapidly evolving technologies are set to intersect at the crossroads of the future of medicine: the knowledge of how to induce and maintain cellular pluripotency, and the ability to precisely manipulate the genome with engineered nucleases. Together, these two advances have significant potential in the development of the next generation of cell and gene therapies. This review will discuss human and animal models of stem cells and the application of engineered nucleases for precision gene targeting and control. For animal studies and models, nucleases have allowed for greater flexibility and expandability. Previously untargetable regions of the murine genome are now accessible via engineered nucleases. Prior to the availability of gene editing proteins, the entire rat genome was largely refractory to gene targeting and manipulation. The ability to engineer larger animals may reduce the transplant organ gap and increase the yields of food for an expanding population. Lastly, the ability to modify stem cells of hematopoietic, embryonic, or somatic origin will allow for more relevant disease modeling, and more targeted and effective therapies. Collectively, the efficiency of gene editing nucleases and the ability to apply them across cells of multiple species allows for new research opportunities, more flexibility, and greater accuracy in choosing the model best suited for genome manipulation.

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Acknowledgements

M.J.O. is supported by funding from the Lindahl Family and the Corrigan Family. J.T. is supported by grants from the National Institutes of Health (R01 AR063070 and R01 AR059947), the Department of Defense (USAMRAA/DOD Dept of the Army W81XWH-12-1-0609 and USAMRAA/DOD W81XWH-10-1-0874), DebRA International, Sohana Research Fund, Richard M. Schulze Family Foundation, Jackson Gabriel Silver Fund, Epidermolysis Bullosa Medical Research Fund, and University of Pennsylvania grant MPS I-11-009-01. M.J.O. and J.T. are also supported by the Children’s Cancer Research Fund, Minnesota. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (M.J.O.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Pediatrics, Division of Blood and Marrow Transplantation, Masonic Cancer Center, Stem Cell Institute, and Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA

    Mark J. Osborn Ph.D.

  2. Department of Pediatrics, Division of Blood and Marrow Transplantation, Stem Cell Institute, University of Minnesota, MMC 366, 420 Delaware Street SE, Minneapolis, MN, 55455, USA

    Jakub Tolar M.D., Ph.D.

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  1. Mark J. Osborn Ph.D.
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Correspondence to Jakub Tolar M.D., Ph.D. .

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  1. Inst for Cell & Gene Therapy, Universitaetsklinikum Freiburg, Freiburg, Baden-Württemberg, Germany

    Toni Cathomen

  2. University of North Carolina, Chapel Hill, North Carolina, USA

    Matthew Hirsch

  3. Stanford Medical School, Palo Alto, California, USA

    Matthew Porteus

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Osborn, M.J., Tolar, J. (2016). Cellular Engineering and Disease Modeling with Gene-Editing Nucleases. In: Cathomen, T., Hirsch, M., Porteus, M. (eds) Genome Editing. Advances in Experimental Medicine and Biology(). Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3509-3_12

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