Gene modulation for treating liver fibrosis

Kun Cheng, Ram I. Mahato

Research output: Contribution to journalReview article

31 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)93-146
Number of pages54
JournalCritical Reviews in Therapeutic Drug Carrier Systems
Volume24
Issue number2
DOIs
StatePublished - Jan 1 2007

Fingerprint

Liver Cirrhosis
Nucleic Acids
Genes
Antisense RNA
Hepatic Stellate Cells
RNA Interference
Oligonucleotides
Extracellular Matrix
Proteins
Molecular Weight
Cytokines
Inflammation
Liver
Wounds and Injuries
Therapeutics
Pharmaceutical Preparations

Keywords

  • Antigene
  • Antisense
  • Gene modulation
  • Hepatic stellate cells
  • Liver fibrosis
  • Triplex-forming oligonucleotide
  • siRNA

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Gene modulation for treating liver fibrosis. / Cheng, Kun; Mahato, Ram I.

In: Critical Reviews in Therapeutic Drug Carrier Systems, Vol. 24, No. 2, 01.01.2007, p. 93-146.

Research output: Contribution to journalReview article

@article{982671ed63d749d3ad674563a08085d9,
title = "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.",
keywords = "Antigene, Antisense, Gene modulation, Hepatic stellate cells, Liver fibrosis, Triplex-forming oligonucleotide, siRNA",
author = "Kun Cheng and Mahato, {Ram I.}",
year = "2007",
month = "1",
day = "1",
doi = "10.1615/CritRevTherDrugCarrierSyst.v24.i2.10",
language = "English (US)",
volume = "24",
pages = "93--146",
journal = "Critical Reviews in Therapeutic Drug Carrier Systems",
issn = "0743-4863",
publisher = "Begell House Inc.",
number = "2",

}

TY - JOUR

T1 - Gene modulation for treating liver fibrosis

AU - Cheng, Kun

AU - Mahato, Ram I.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - 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.

AB - 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.

KW - Antigene

KW - Antisense

KW - Gene modulation

KW - Hepatic stellate cells

KW - Liver fibrosis

KW - Triplex-forming oligonucleotide

KW - siRNA

UR - http://www.scopus.com/inward/record.url?scp=34548229993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548229993&partnerID=8YFLogxK

U2 - 10.1615/CritRevTherDrugCarrierSyst.v24.i2.10

DO - 10.1615/CritRevTherDrugCarrierSyst.v24.i2.10

M3 - Review article

C2 - 17725523

AN - SCOPUS:34548229993

VL - 24

SP - 93

EP - 146

JO - Critical Reviews in Therapeutic Drug Carrier Systems

JF - Critical Reviews in Therapeutic Drug Carrier Systems

SN - 0743-4863

IS - 2

ER -