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. 2021 Jan 20;22(3):1022.
doi: 10.3390/ijms22031022.

Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

Tatyana P Makalish  1 , Ilya O Golovkin  1 , Volodymyr V Oberemok  2   3 , Kateryna V Laikova  2   4 , Zenure Z Temirova  1 , Olesya A Serdyukova  2 , Ilya A Novikov  2   4 , Roman A Rosovskyi  2 , Andrey I Gordienko  1 , Evgeniya Yu Zyablitskaya  1 , Elvina A Gafarova  1 , Kseniya A Yurchenko  1 , Iryna I Fomochkina  1 , Anatoly V Kubyshkin  1
Affiliations

Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

Tatyana P Makalish et al. Int J Mol Sci. .

Abstract

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund's adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

Keywords: Humira®; TNF-α; antisense technologies; inflammation; phosphorothioate oligonucleotides; rheumatoid arthritis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Left hind paws of rats. (a) Sham; (b,c) control after 7 and 21 days, respectively; (d–f) 7, 14, and 21 days after treatment with Cytos-11, respectively; (g–i) 7, 14, and 21 days after treatment with Humira, respectively.
Figure 2
Figure 2
Hematoxylin–eosin-stained rat metatarsophalangeal joints from different periods during the experiment (used 5× lens); (a) sham; (b,c) control after 7 and 21 days, respectively; (d–f) 7, 14, and 21 days after treatment with Cytos-11, respectively; (g–i) 7, 14, and 21 days after treatment with Humira, respectively. Thick arrows indicate destructive changes in the joints and synovial hyperplasia. Thin arrows show the restoration of the normal structure of the synovium. P—pannus, S—synovial membrane, JC—joint cartilage.
Figure 3
Figure 3
Synovial membrane of the metatarsophalangeal joints. Immunohistochemical staining with antibodies against TNF-α. Magnification 40×. (a) Sham; (b,c) control after 7 and 21 days; (d–f) 7, 14, and 21 days after treatment with Cytos-11; (g–i) 7, 14, and 21 days after treatment with Humira. L—lymphocytes, M—macrophages, S—synoviocytes, V—vascular endothelium. Red arrows indicate high TNF-α expression in untreated groups as well as early treatment with Cytos-11 and Humira. White arrows indicate a decrease in TNF-α expression.
Figure 4
Figure 4
Dynamics of changes in the concentration of TNF-α in peripheral blood in different groups of the experiment. * Significant differences compared to the control group. I—error of the mean.
See this image and copyright information in PMC

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