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Critical Reviews™ in Therapeutic Drug Carrier Systems
IF: 2.9 5-Year IF: 3.72 SJR: 0.736 SNIP: 0.551 CiteScore™: 2.43

ISSN Print: 0743-4863
ISSN Online: 2162-660X

Volumes:
Volume 36, 2019 Volume 35, 2018 Volume 34, 2017 Volume 33, 2016 Volume 32, 2015 Volume 31, 2014 Volume 30, 2013 Volume 29, 2012 Volume 28, 2011 Volume 27, 2010 Volume 26, 2009 Volume 25, 2008 Volume 24, 2007 Volume 23, 2006 Volume 22, 2005 Volume 21, 2004 Volume 20, 2003 Volume 19, 2002 Volume 18, 2001 Volume 17, 2000 Volume 16, 1999 Volume 15, 1998 Volume 14, 1997 Volume 13, 1996 Volume 12, 1995

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

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.