Published 6 issues per year
ISSN Print: 0743-4863
ISSN Online: 2162-660X
Indexed in
Gene Modulation for Treating Liver Fibrosis
ABSTRACT
Despite tremendous progress in our understanding of fibrogenesis, injury stimuli process, inflammation, and hepatic stellate cell (HSC) activation, there is still no standard treatment for liver fibrosis. Delivery of small molecular weight drugs, proteins, and nucleic acids to specific liver cell types remains a challenge due to the overexpression of extracellular matrix (ECM) and consequent closure of sinusoidal gaps. In addition, activation of HSCs and subsequent release of inflammatory cytokines and infiltration of immune cells are other major obstacles to the treatment of liver fibrosis. To overcome these barriers, different therapeutic approaches are being investigated. Among them, the modulation of certain aberrant protein production is quite promising for treating liver fibrosis. In this review, we describe the mechanism of antisense, antigene, and RNA interference (RNAi) therapies and discuss how the backbone modification of oligonucleotides affects their in vivo stability, biodistribution, and bioactivity. Strategies for delivering these nucleic acids to specific cell types are discussed. This review critically addresses various insights developed with each individual strategy and for multipronged approaches, which will be helpful in achieving more effective outcomes.
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Jain Akshay, Barve Ashutosh, Zhao Zhen, Fetse John Peter, Liu Hao, Li Yuanke, Cheng Kun, Targeted Delivery of an siRNA/PNA Hybrid Nanocomplex Reverses Carbon Tetrachloride‐Induced Liver Fibrosis, Advanced Therapeutics, 2, 8, 2019. Crossref
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Wu Pengkai, Luo Xinping, Wu Hui, Zhang Qingyan, Dai Yuanxin, Sun Minjie, Efficient and targeted chemo-gene delivery with self-assembled fluoro-nanoparticles for liver fibrosis therapy and recurrence, Biomaterials, 261, 2020. Crossref
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Wu Pengkai, Luo Xinping, Sun Meiling, Sun Beicheng, Sun Minjie, Synergetic regulation of kupffer cells, extracellular matrix and hepatic stellate cells with versatile CXCR4-inhibiting nanocomplex for magnified therapy in liver fibrosis, Biomaterials, 284, 2022. Crossref
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Li Chunxue, Zhan Yating, Zhang Rongrong, Tao Qiqi, Lang Zhichao, Zheng Jianjian, 20(S)- Protopanaxadiol suppresses hepatic stellate cell activation via WIF1 demethylation-mediated inactivation of the Wnt/β-catenin pathway, Journal of Ginseng Research, 2022. Crossref