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Critical Reviews™ in Therapeutic Drug Carrier Systems
Facteur d'impact: 2.9 Facteur d'impact sur 5 ans: 3.72 SJR: 0.573 SNIP: 0.551 CiteScore™: 2.43

ISSN Imprimer: 0743-4863
ISSN En ligne: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v24.i2.10
pages 93-146

Gene Modulation for Treating Liver Fibrosis

Kun Cheng
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163
Ram I. Mahato
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 26 S. Dunlap Street, Feurt Building, Room 406, Memphis TN 38163, USA

RÉSUMÉ

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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