Research output: Contribution to journal › Article › peer-review
Cholesterol-Modified Anti-Il6 siRNA Reduces the Severity of Acute Lung Injury in Mice. / Chernikov, Ivan V.; Bachkova, Irina K.; Sen’kova, Aleksandra V. et al.
In: Cells, Vol. 13, No. 9, 767, 05.2024.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Cholesterol-Modified Anti-Il6 siRNA Reduces the Severity of Acute Lung Injury in Mice
AU - Chernikov, Ivan V.
AU - Bachkova, Irina K.
AU - Sen’kova, Aleksandra V.
AU - Meschaninova, Mariya I.
AU - Savin, Innokenty A.
AU - Vlassov, Valentin V.
AU - Zenkova, Marina A.
AU - Chernolovskaya, Elena L.
N1 - This research was funded by the Russian Science Foundation (grant №19-74-30011) and project ICBFM SB RAS №121031300044-5 (synthesis of control siRNAs).
PY - 2024/5
Y1 - 2024/5
N2 - 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 their 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.
AB - 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 their 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.
KW - IL6
KW - LPS
KW - acute lung injury
KW - chemically modified siRNA
KW - inflammation
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85192726012&origin=inward&txGid=5709f63c155e8f5cdde540b9d6e3cd31
UR - https://www.mendeley.com/catalogue/0695898e-0d1f-3007-ac73-d28a59dc0015/
U2 - 10.3390/cells13090767
DO - 10.3390/cells13090767
M3 - Article
C2 - 38727303
VL - 13
JO - Cells
JF - Cells
SN - 2073-4409
IS - 9
M1 - 767
ER -
ID: 61051062