A new era of genetic engineering for autoimmune and inflammatory diseases

Chronic autoimmune and inflammatory diseases exhibit variable genetic factors. The tools for specific and efficient genetic engineering are developing at a dramatic pace and are now being applied to therapy of human diseases. Gene editing tools can be used to interdict the pathology of inflammation at multiple stages. Therapies utilizing genetically modified cells offer many potential advantages over traditional cellular therapy approaches. Monogenic autoinflammatory disease, loss of self-tolerance, autoimmune disease based in humoral immunity, and regenerative medicine for tissues deranged or destroyed by inflammation are potential pathologies that could be treated with therapies based in genetic editing technologies. In this review, we discuss the rapid evolution of technologies for genome editing and their applications for autoimmune and inflammatory diseases. We compare older-generation methods, including zinc-finger nucleases and transcription activator-like effector nucleases, with more-recently developed tools, mainly CRISPR/Cas9. Gene-editing tool delivery methods including viral vectors and non-viral technologies are summarized. Finally, pre-clinical experiments with gene editing for therapy of animal models of autoimmune and inflammatory disease, and initial experience with gene-edited cells in human autoimmunity are described. In this review, we discuss potential therapeutic uses of chimeric autoantigen receptor T cells and regulatory T cells for polygenic disease, genetically-modified hematopoietic stem and progenitor cell transplantation for monogenic disease, and modified induced pluripotent stem cells for regenerative medicine.