Lipid Nanoparticle‐Mediated Delivery of CRISPR‐Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism
Abstract: Non‐alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon‐specific CRISPR‐Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism‐related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Lipid Nanoparticle‐Mediated Delivery of CRISPR‐Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism ; day:18 ; month:06 ; year:2024 ; extent:12
Advanced science ; (18.06.2024) (gesamt 12)
- Creator
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Bai, Yu
Nan, Yanyang
Wu, Tao
Zhu, An
Xie, Xinlei
Sun, Yun
Deng, Yong
Dou, Zihan
Hu, Xiaozhi
Zhou, Rongrui
Xu, Shuwen
Zhang, Yuanzhen
Fan, Jiajun
Ju, Dianwen
- DOI
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10.1002/advs.202400493
- URN
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urn:nbn:de:101:1-2406191442322.809662855312
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:54 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Bai, Yu
- Nan, Yanyang
- Wu, Tao
- Zhu, An
- Xie, Xinlei
- Sun, Yun
- Deng, Yong
- Dou, Zihan
- Hu, Xiaozhi
- Zhou, Rongrui
- Xu, Shuwen
- Zhang, Yuanzhen
- Fan, Jiajun
- Ju, Dianwen
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