RNA therapeutics in rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis: a compartment-aware translational framework
- 1NOBELab (Nucleosides, Oligonucleotides, and Biological Evaluation Laboratory), Division of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Qarabağ University
- 2Division of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Qarabağ University
- 3Division of Internal Medicine, Faculty of Medicine and Health Sciences, Qarabağ University
Abstract
Rheumatoid arthritis (RA), systemic lupus erythematosus/lupus nephritis (SLE/LN), and systemic sclerosis (SSc) remain major causes of chronic inflammation, disability, organ damage, and treatment burden despite therapeutic advances. 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. SSc combines strong antifibrotic RNA biology with an accessible skin proof-of-mechanism window, whereas lung, vascular, and internal-organ programs remain more delivery-limited. We separate human pathway validation, RNA-platform evidence outside the target disease, disease-specific RNA evidence, and patient efficacy. Recent human complement-factor-B pharmacodynamic data strengthen the platform-level evidence but do not establish efficacy in RA or LN. The most informative early trials will therefore be biomarker-enriched and mechanism-rich, with prespecified criteria that distinguish target failure from delivery, dose, endotype, or safety failure.
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BibTeX
@article{afandizada2026therapeutics,
title = {{RNA therapeutics in rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis: a compartment-aware translational framework}},
author = {Yusif Afandizada and Hikmet Memmedov and Mushfig Orujov and Shahla Eyvazova and Shirkhan Amikishiyev},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1950465},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1950465/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - RNA therapeutics in rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis: a compartment-aware translational framework
AU - Yusif Afandizada
AU - Hikmet Memmedov
AU - Mushfig Orujov
AU - Shahla Eyvazova
AU - Shirkhan Amikishiyev
PY - 2026
DA - 2026/10/05
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1950465
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1950465/full
AB - Rheumatoid arthritis (RA), systemic lupus erythematosus/lupus nephritis (SLE/LN), and systemic sclerosis (SSc) remain major causes of chronic inflammation, disability, organ damage, and treatment burden despite therapeutic advances. 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. SSc combines strong antifibrotic RNA biology with an accessible skin proof-of-mechanism window, whereas lung, vascular, and internal-organ programs remain more delivery-limited. We separate human pathway validation, RNA-platform evidence outside the target disease, disease-specific RNA evidence, and patient efficacy. Recent human complement-factor-B pharmacodynamic data strengthen the platform-level evidence but do not establish efficacy in RA or LN. The most informative early trials will therefore be biomarker-enriched and mechanism-rich, with prespecified criteria that distinguish target failure from delivery, dose, endotype, or safety failure.
SN - 1664-3224
ER -