Fatemeh Safari1,2,3, Safar Farajnia4, Maryam Arya5, Habib Zarredar6, Ava Nasrolahi7. 1. a Department of Medical Biotechnology, Faculty of Advanced Medical Sciences , Tabriz University of Medical Sciences , Tabriz , Iran. 2. b Student Research Committee , Tabriz University of Medical Sciences , Tabriz , Iran. 3. c Department of Medical Biotechnology , Shiraz University of Medical Sciences , Shiraz , Iran. 4. d Biotechnology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran. 5. e Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz , Iran. 6. f Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences , Tabriz , Iran. 7. g Molecular Medicine Department, Faculty of Advanced Medical Sciences , Tabriz University of Medical Sciences , Tabriz , Iran.
Abstract
INTRODUCTION: Rheumatoid arthritis (RA), as one of the most disabling autoimmune diseases, is a common health problem that progressively reduces the life quality of patients. Although various biologics have been introduced for RA, attempts to establish an efficient long-term therapies failed due to the heterogeneity of this disease. METHODS: In the last decade, immunomodulatory approaches such as T cell adoptive therapy have been developed for controlling autoimmunity. Regulatory T cells (Tregs), the major self-tolerance mediator, are crucial for down-regulation of aberrant immune stimulations. Hence, recruiting ex vivo Tregs emerged as a promising therapy for a variety of autoimmune diseases. RESULTS: The major bottleneck of the Treg adoptive therapy is maintaining the in vivo stability and plasticity of these fascinating cells. Recent progress in genome editing technology clustered regularly interspaced short palindromic repeats (CRISPR) in combination with CRISPR-associated (Cas) 9 system provided a new solution for this bottleneck. CONCLUSIONS: The present paper discusses RA pathogenesis and the potential application of new developments in CRISPR-mediated Treg genome editing in personalized therapy of RA.
INTRODUCTION:Rheumatoid arthritis (RA), as one of the most disabling autoimmune diseases, is a common health problem that progressively reduces the life quality of patients. Although various biologics have been introduced for RA, attempts to establish an efficient long-term therapies failed due to the heterogeneity of this disease. METHODS: In the last decade, immunomodulatory approaches such as T cell adoptive therapy have been developed for controlling autoimmunity. Regulatory T cells (Tregs), the major self-tolerance mediator, are crucial for down-regulation of aberrant immune stimulations. Hence, recruiting ex vivo Tregs emerged as a promising therapy for a variety of autoimmune diseases. RESULTS: The major bottleneck of the Treg adoptive therapy is maintaining the in vivo stability and plasticity of these fascinating cells. Recent progress in genome editing technology clustered regularly interspaced short palindromic repeats (CRISPR) in combination with CRISPR-associated (Cas) 9 system provided a new solution for this bottleneck. CONCLUSIONS: The present paper discusses RA pathogenesis and the potential application of new developments in CRISPR-mediated Treg genome editing in personalized therapy of RA.
Authors: Molly Klimak; Robert J Nims; Lara Pferdehirt; Kelsey H Collins; Natalia S Harasymowicz; Sara J Oswald; Lori A Setton; Farshid Guilak Journal: Acta Biomater Date: 2021-04-03 Impact factor: 8.947