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RAS BiologyБиохимия Biochemistry

  • ISSN (Print) 0320-9725
  • ISSN (Online) 3034-5294

SUPPRESSION OF AND GENE EXPRESSION BY SYNTHETIC SIRNA MOLECULES REDUCES NASAL HYPERREACTIVITY AND INFLAMMATION IN A MOUSE MODEL OF ALLERGIC RHINITIS

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PII
S30345294S0320972525040039-1
DOI
10.7868/S3034529425040039
Publication type
Article
Status
Published
Authors
M.M. Kaganova
  • Affiliation: Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
I.P. Shilovskiy
  • Affiliation: Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
V.I. Kovchina
  • Affiliation: Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
E.D. Timotievich
  • Affiliation: Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
T.E. Rusak
  • Affiliation: Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
A.A. Nikolskii
  • Affiliation: Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
K.V. Yumashev
  • Affiliation: Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
G.B. Pasikhov
  • Affiliation: Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
K.V. Vinogradova
  • Affiliation:
    Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
    MVA named after K. I. Skryabin of the Ministry of Agriculture of the Russian Federation, Moscow State Academy of Veterinary Medicine and Biotechnology
D.A. Gurskii
  • Affiliation:
    Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
    MVA named after K. I. Skryabin of the Ministry of Agriculture of the Russian Federation, Moscow State Academy of Veterinary Medicine and Biotechnology
M.V. Popova
  • Affiliation:
    Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
    Pirogov Russian National Research Medical University Ministry of Health of the Russian Federation
V.E. Brylina
  • Affiliation: MVA named after K. I. Skryabin of the Ministry of Agriculture of the Russian Federation, Moscow State Academy of Veterinary Medicine and Biotechnology
M.R. Khaitov
  • Affiliation:
    Institute of Immunology of the Federal Medical-Biological Agency, National Research Center
    Pirogov Russian National Research Medical University Ministry of Health of the Russian Federation
Volume/ Edition
Volume 90 / Issue number 4
Pages
531-549
Abstract
Th2 cytokines (IL-4, IL-5, and IL-13) play an important role in the development of allergies, including allergic rhinitis (AR). IL-13 promotes mucus hypersecretion in the airways and IL-5 recruits eosinophils to the nasal mucosa, leading to increased inflammation and tissue damage. Drugs based on monoclonal antibodies that block the activity of these cytokines are being developed for the treatment of allergic diseases. However, studies of drugs that target IL-13 alone (such as Trabokinumab and Lebrikizumab) were not successful. Given that IL-5 and IL-13 have different roles in AR, simultaneous inhibition of both cytokines may be a promising approach. New methods of regulating gene activity, such as RNA interference (RNAi), offer new perspectives for the development of drugs. This study describes a complex consisting of siRNAs that inhibit the activity of or genes and a carrier peptide LTP. The effects of this complex on the allergic inflammation in a mouse model of AR was studied. Suppression of expression decreased nasal hyperreactivity and reduced the number of goblet cells in the respiratory epithelium of AR-induced mice. Inhibiting the gene had a more beneficial effect than suppression alone, further contributing to reducing the number of cells infiltration the nasal cavity. When both and were suppressed simultaneously, the result was similar to that of inhibition alone. Likely, IL-13 plays a more significant role in the development of AR than IL-5. As a result, the possibility of using RNAi for anti-cytokine therapy for AR has been demonstrated. However, dual inactivation of IL-5 and IL-13 by siRNAs does not provide any advantages over inactivating IL-13 alone in the current mouse model of AR. However, the lack of success of anti-IL-13 therapy in clinical practice indicates the promise of an approach based on the dual blocking of IL-5 and IL-13.
Keywords
аллергия цитокины РНК-интерференция IL-5 IL-13 Th2-иммунный ответ
Date of publication
28.04.2025
Year of publication
2025
Number of purchasers
0
Views
114

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