A CRISPR-based approach to targeting a pathogenic TLR7 gene variant in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease where the body's immune system becomes highly sensitive to non-pathogenic ssRNA, triggering an immune attack on healthy tissue. This incites inflammation, tissue damage, and life-long, adverse side effects. Research has linked over 50 genes to SLE, including the TLR7 gene, which is often overexpressed in individuals with SLE. Recently, a pathogenic variant of the TLR7 gene, known as TLR7-Y264H was demonstrated to oversensitize the toll-like receptors in the cell, resulting in the symptoms of SLE. There is a significant gap in research for SLE treatments, as current options often fail to provide long-term disease control with minimal toxicity. Therefore, this study explores a CRISPR-based approach to rectify this pathogenic variant of TLR7. In light of recent research highlighting the role of TLR7-Y264H mutation’s overexpression in SLE patients, this study investigates whether a CRISPR-based therapeutic approach can effectively dampen SLE symptoms.