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Gene editing for inflammatory disorders
  1. David T Ewart1,
  2. Erik J Peterson1,
  3. Clifford J Steer2,3
  1. 1Division of Rheumatic and Autoimmune Diseases, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
  2. 2Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
  3. 3Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, Minnesota, USA
  1. Correspondence to Dr David T Ewart, Division of Rheumatic and Autoimmune Diseases, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA; ewar0001{at}umn.edu and Dr Clifford J Steer, Departments of Medicine and Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, MN 55455, USA; steer001{at}umn.edu

Abstract

Technology for precise and efficient genetic editing is constantly evolving and is now capable of human clinical applications. Autoimmune and inflammatory diseases are chronic, disabling, sometimes life-threatening, conditions that feature heritable components. Both primary genetic lesions and the inflammatory pathobiology underlying these diseases represent fertile soil for new therapies based on the capabilities of gene editing. The ability to orchestrate precise targeted modifications to the genome will likely enable cell-based therapies for inflammatory diseases such as monogenic autoinflammatory disease, acquired autoimmune disease and for regenerative medicine in the setting of an inflammatory environment. Here, we discuss recent advances in genome editing and their evolving applications in immunoinflammatory diseases. Strengths and limitations of older genetic modification tools are compared with CRISPR/Cas9, base editing, RNA editing, targeted activators and repressors of transcription and targeted epigenetic modifiers. Commonly employed delivery vehicles to target cells or tissues of interest with genetic modification machinery, including viral, non-viral and cellular vectors, are described. Finally, applications in animal and human models of inflammatory diseases are discussed. Use of chimeric autoantigen receptor T cells, correction of monogenic diseases with genetically edited haematopoietic stem and progenitor cells, engineering of induced pluripotent stem cells and ex vivo expansion and modification of regulatory T cells for a range of chronic inflammatory diseases are reviewed.

  • inflammation
  • autoimmunity
  • autoimmune diseases

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors All authors contributed to the conception and design as well as the literature review for this work. Each participated in drafting and revising the important intellectual content and approved the final version to be published. All are accountable for all aspects of this work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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