Restoring Healthy Phenotypes in Juvenile Idiopathic Arthritis Through Targeted Manipulation of the HLA-DRB1 Gene
DOI:
https://doi.org/10.58445/rars.3362Keywords:
Juvenile Idiopathic Arthritis, HLA-DRB1, Gene Editing, Amino Acid Polymorphism, Autoimmune Disease, CRISPR-Cas9, Immunogenetics, Peptide Binding Groove, Autoimmune Disorders, Chronic Inflammation, Rheumatology, Inflmmation, Autoimmune DisorderAbstract
Juvenile Idiopathic Arthritis (JIA) is a chronic autoimmune disease with poorly understood genetic factors and often life-lasting treatment and implications. This review investigates the potential of gene editing on the Human Leukocyte Antigens (HLA-DRB1) gene, particularly on altering amino acids 11 and 13 to restore a healthy phenotype in JIA patients. Genetic associations, JIA pathophysiology, and therapeutic implications were evaluated by conducting a literature review of papers from PubMed, Science Direct, and National Institutes of Health (NIH). Key findings include that positions 11 and 13 significantly influence peptide binding grooves and antigen presentation that lead to JIA, yet editing these genes for therapeutic purposes is highly theoretical. The hyperpolymorphic nature of HLA genes, difficulty of editing precisions, challenges with delivery, and ethical concerns mean clinical application with current gene editing technologies is not yet feasible for JIA. However, progress with technologies like CRISPR and PRIME editing shows that what remains currently unattainable may become a realistic possibility in the future.
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