Table 1_RNA therapeutics in rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis: a compartment-aware translational framework.docx

RNA therapeutics offer programmable transcript suppression, network-level microRNA modulation, transient restoration of protective proteins, and targeting-ligand functions. Existing reviews largely catalogue modalities or individual delivery systems; this review instead asks whether a candidate forms an interpretable translational program across target biology, disease compartment, intended cell, productive intracellular access, direct target engagement, pathway pharmacodynamics, repeat-dose safety, and manufacturing feasibility.

RA is primarily a synovial immune–stromal delivery problem in which RNA programs must also demonstrate an advantage over effective biologic or targeted synthetic therapies. SLE/LN offers interferon, B-cell, co-stimulatory, microRNA, messenger RNA (mRNA), and complement opportunities, but therapeutic nucleic acids and carriers must not intensify nucleic-acid sensing, interferon activity, or complement-associated injury.