Applications of CRISPR in the Treatment of Autoimmune Diseases

Abstract

Autoimmune disorders are marked by the immune system’s erroneous recognition and ongoing assault on the body’s own tissues, impacting roughly 5-10% of individuals. Existing interventions, such as immunosuppressive drugs, can ease outward symptoms but cannot eliminate the root cause, while long-term use may bring about risks like heightened infection susceptibility or organ damage due to toxicity. CRISPR gene editing technology, which allows for accurate genomic modifications through Cas9 endonuclease and programmable guide RNA, has exhibited potential in treating monogenic diseases and certain tumors. However, its use in complex autoimmune conditions is still in the early investigative stage, with current approaches centered on editing genes that regulate immune cell activity and reestablishing immune tolerance. Notable research limitations include inefficient cell-type-specific delivery systems, unaddressed off-target modifications, and insufficient verification of long-term safety. This study conducts a comprehensive assessment of CRISPR-based therapeutic strategies for autoimmune diseases, encompassing the identification of disease-related genes (e.g., TLR7 in SLE and PTPN22 in RA), editing techniques (gene knockout, knock-in, and base editing), and the regulation of immune cell functions. Preclinical results show reduced production of autoantibodies, inhibited inflammatory responses, and mitigated tissue harm in models of SLE and RA. These findings offer a scientific foundation for the development of targeted, curative treatments, overcoming the drawbacks of traditional therapies. Future investigations should focus on improving editing accuracy, refining delivery systems, and performing extended safety evaluations to expedite the clinical application of personalized CRISPR-based treatments for autoimmune disorders.