Cholesterol-Modified Anti-Il6 siRNA Reduces the Severity of Acute Lung Injury in Mice

Ivan V. Chernikov; Irina K. Bachkova; Aleksandra V. Sen’kova; Mariya I. Meschaninova; Innokenty A. Savin; Valentin V. Vlassov; Marina A. Zenkova; Elena L Chernolovskaya

doi:10.20944/preprints202404.1195.v1

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preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202404.1195.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cholesterol-Modified Anti-Il6 siRNA Reduces the Severity of Acute Lung Injury in Mice

Ivan V. Chernikov

Irina K. Bachkova

Aleksandra V. Sen’kova

Mariya I. Meschaninova

Innokenty A. Savin

Valentin V. Vlassov

Marina A. Zenkova

Elena L Chernolovskaya

Version 1 : Received: 17 April 2024 / Approved: 17 April 2024 / Online: 18 April 2024 (14:20:50 CEST)

A peer-reviewed article of this Preprint also exists.

Chernikov, I.V.; Bachkova, I.K.; Sen’kova, A.V.; Meschaninova, M.I.; Savin, I.A.; Vlassov, V.V.; Zenkova, M.A.; Chernolovskaya, E.L. Cholesterol-Modified Anti-Il6 siRNA Reduces the Severity of Acute Lung Injury in Mice. Cells 2024, 13, 767. Chernikov, I.V.; Bachkova, I.K.; Sen’kova, A.V.; Meschaninova, M.I.; Savin, I.A.; Vlassov, V.V.; Zenkova, M.A.; Chernolovskaya, E.L. Cholesterol-Modified Anti-Il6 siRNA Reduces the Severity of Acute Lung Injury in Mice. Cells 2024, 13, 767.

Abstract

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Keywords

acute lung injury; inflammation; chemically modified siRNA; IL6; LPS

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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