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Transl Res. 2019 Dec;214:1-16. doi: 10.1016/j.trsl.2019.07.002. Epub 2019 Jul 10.

Applications of RNA interference in the treatment of arthritis.

Author information

1
Department of Orthopedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, Missouri; Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, Missouri.
2
Department of Cardiovascular Sciences, University of South Florida Health Heart Institute, Morsani School of Medicine, Tampa, Florida.
3
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
4
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: cpham@wustl.edu.

Abstract

RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy holds significant promise for the treatment of a wide-range of arthritic diseases. siRNA selectively suppresses the expression of a gene product and can thus achieve the specificity that is lacking in small molecule inhibitors. The potential use of siRNA-based therapy in arthritis, however, has not progressed to clinical trials despite ample evidence for efficacy in preclinical studies. One of the main challenges to clinical translation is the lack of a suitable delivery vehicle to efficiently and safely access diverse pathologies. Moreover, the ideal targets in treatment of arthritides remain elusive given the complexity and heterogeneity of these disease pathogeneses. Herein, we review recent preclinical studies that use RNAi-based drug delivery systems to mitigate inflammation in models of rheumatoid arthritis and osteoarthritis. We discuss a self-assembling peptide-based nanostructure that demonstrates the potential of overcoming many of the critical barriers preventing the translation of this technology to the clinic.

PMID:
31351032
PMCID:
PMC6848781
[Available on 2020-12-01]
DOI:
10.1016/j.trsl.2019.07.002

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