Nucleic Acid-based Therapy in Effective Management of Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is a chronic autoimmune disease that prominently affects the joints of the body, including one or more types, such as wrists, knees, fingers, and toes. This condition is characterized by specific auto-immune responses, i.e., inflammation, swelling, stiffness, and pain in the body's joints. This results in partial or complete immobility. Several treatment options are available in the pharmaceutical market, commonly immunosuppressants, anti-inflammatory drugs, corticosteroids, anti-antibody drugs, etc. However, such drug treatments provide only symptomatic relief and lack long-term therapeutic efficacy. Thus, there is a need to develop an alternative treatment option that potentially can cure this disease. Recently, researchers have shifted their focus to targeting the root cause involved in the pathogenesis of RA by designing nucleic-acid- based molecules. With this objective, we have provided this review in which we have explored the nucleic acid-based techniques used to treat RA. Various molecular and genetic methods, including antisense oligonucleotides, small interfering RNA (siRNA), CRISPR-Cas9 gene editing, RNA-based vaccines, microRNA (miRNA) therapeutics, and epigenetic modifications are used to target the mechanisms underlying RA pathogenesis. Through the extensive evaluation of clinical and preclinical studies, we reported nucleic acid-based therapy's clinical efficacy, safety, and therapeutic benefits. In addition, this study states the associated pharmacokinetic challenges followed by approaches to overcome them. Nucleic acid-based therapies are susceptible to degradation by nucleases in the body and are not efficiently absorbed due to their considerable molecular weight. Specialized carriers like nanoparticles are employed for their effective delivery. Nucleic acid-based therapies hold immense potential for achieving more effective, less toxic, and patient-centric management of RA, offering hope for improved outcomes and an enhanced quality of life for individuals living with this challenging autoimmune condition.