A potent and specific morpholino antisense inhibitor of hepatitis C translation in mice

@article{McCaffrey2003APA,
  title={A potent and specific morpholino antisense inhibitor of hepatitis C translation in mice},
  author={Anton P. McCaffrey and Leonard Meuse and Mobin Karimi and Christopher H. Contag and Mark A. Kay},
  journal={Hepatology},
  year={2003},
  volume={38}
}
Hepatitis C virus (HCV) is an RNA virus infecting one in every 40 people worldwide. Current treatments are ineffective and HCV is the leading cause of liver failure leading to transplantation in the United States and Europe. Translational control of HCV is a prime therapeutic target. We assessed the inhibitory potential of morpholino phosphoramidate antisense oligonucleotides (morpholinos) on HCV translation by codelivering them with reporter plasmids expressing firefly luciferase under the… Expand
Antisense Morpholino-Oligomers Directed against the 5′ End of the Genome Inhibit Coronavirus Proliferation and Growth†
TLDR
Conjugation of a peptide related to the human immunodeficiency virus type 1 Tat represents a novel method for delivery of antisense morpholino-oligomers that has therapeutic potential for control of coronavirus infection. Expand
Small hairpin RNAs efficiently inhibit hepatitis C IRES-mediated gene expression in human tissue culture cells and a mouse model.
TLDR
Results indicate that shRNAs, delivered as RNA or expressed from viral or nonviral vectors, may be effective agents for the control of HCV and related viruses. Expand
Suppression of Hepatitis C Viral Genome Replication with RNA-Cleaving Deoxyribozyme
TLDR
The DNAzyme and the DNAzyme conjugated nanoparticle system are discussed in detail to demonstrate a successful usage of functional oligonucleotide and its delivery in vivo for further therapeutic application offunctional oligon nucleotides in the treatment of hepatitis C. Expand
Long-term hepatitis C internal ribosome entry site-dependent gene expression mediated by phage φC31 integrase in mouse model
TLDR
The results indicate that this mouse model provides a powerful tool for accurate and long-term evaluation of potential anti-IRES compounds in vivo, and is utilized to develop a stable, reproducible and easily accessible HCV IRES mouse model. Expand
Short peptide nucleic acids (PNA) inhibit hepatitis C virus internal ribosome entry site (IRES) dependent translation in vitro.
TLDR
The hypothesis that antisense molecules, i.e. short peptide nucleic acids (PNA), could inhibit HCV translation by binding to the highly conserved IIId or IV loop regions of the IRES was tested and PNA molecule was shown to have anti-HCV activity. Expand
Gene Therapy for Hepatitis C Virus Infection
TLDR
Gene therapy strategies against HCV show promise and are likely to be useful when used alone or in combination with small-molecule antiviral drugs. Expand
A chimeric GB virus B with 5′ nontranslated RNA sequence from hepatitis C virus causes hepatitis in tamarins
TLDR
Novel chimeric flaviviruses offer opportunities for new insights into HCV replication mechanisms, while potentially facilitating the evaluation of candidate therapeutics in vivo, and appears to contain virus‐specific replication signals that interact with other sites within the viral genome or with viral proteins. Expand
Hepatitis C virus translation inhibitors targeting the internal ribosomal entry site.
TLDR
An overview of approaches to block HCV IRES IRES function by nucleic acid, peptide, and small molecule ligands is provided andphasis will be given to the IRES subdomain IIa, which currently is the most advanced target for small molecule inhibitors of HCV translation. Expand
Antiviral activity of morpholino oligomers designed to block various aspects of Equine arteritis virus amplification in cell culture.
TLDR
The antiviral efficacy of ten antisense phosphorodiamidate morpholino oligomers directed against Equine arteritis virus was evaluated and it is suggested that these compounds could be useful as reagents for exploring the molecular mechanics of nidovirus translation and have anti-EAV potential at relatively low concentrations. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 32 REFERENCES
Determinants of hepatitis C translational initiation in vitro, in cultured cells and mice.
Hepatitis C virus (HCV) is an RNA virus infecting 1 in every 40 people worldwide. Development of new therapeutics for treating HCV has been hampered by the lack of small-animal models. We haveExpand
Targeted inhibition of hepatitis C virus-directed gene expression in human hepatoma cell lines.
TLDR
Antisense oligonucleotides that bind to the NTR of HCV can be targeted by receptor-mediated endocytosis, and they specifically inhibit HCV-directed protein synthesis under intracellular conditions. Expand
Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes
TLDR
Investigation of inhibition of HCV gene expression using antisense oligonucleotides complementary to the 5' NCR, translation initiation codon, and core protein coding sequences found them to be the most effective at inhibiting HCv gene expression, and demonstrates that it is feasible to design antisenseligonucleotide inhibitors of translation that do not require RNase H activation. Expand
Specific inhibition of hepatitis C viral gene expression by antisense phosphorothioate oligodeoxynucleotides
TLDR
The data suggest that HCV gene expression can be inhibited effectively by antisense S‐ODN, and this approach represents a promising perspective for the treatment of hepatitis C. Expand
Antisense Oligonucleotide Inhibition of Hepatitis C Virus (HCV) Gene Expression in Livers of Mice Infected with an HCV-Vaccinia Virus Recombinant
TLDR
Inhibition of HCV reporter gene expression in this small-animal model suggests that antisense oligonucleotides may provide a novel therapy for treatment of chronic HCV infection. Expand
Specific inhibition of hepatitis C viral gene expression by antisense phosphorothioate oligodeoxynucleotides.
TLDR
The data suggest that HCV gene expression can be inhibited effectively by antisense S-ODN, and this approach represents a promising perspective for the treatment of hepatitis C. Expand
Inhibition of hepatitis C virus (HCV)‐RNA–dependent translation and replication of a chimeric HCV poliovirus using synthetic stabilized ribozymes
TLDR
Treatment with synthetic stabilized anti‐HCV ribozymes has the potential to aid patients who are infected with HCV by reducing the viral burden through specific targeting and cleavage of the viral genome. Expand
Inhibition of hepatitis C virus-directed gene expression by a DNA ribonuclease.
TLDR
DNA ribonucleases directed against the HCV genome can specifically cleave target HCV RNA, and modifications of the extreme 3'- and 5'-termini protect against nuclease degradation without appreciable reduction in inhibitory activity against viral gene expression under intracellular conditions. Expand
Enhanced antiviral effect in cell culture of type 1 interferon and ribozymes targeting HCV RNA
TLDR
The results demonstrate that IFN and ribozyme each have a beneficial antiviral effect that is augmented when given in combination. Expand
Cell cycle regulation of hepatitis C virus internal ribosomal entry site-directed translation.
TLDR
These findings suggest that HCV translation is regulated by cellular proteins that vary in abundance during the cell cycle and that viral translation may be enhanced by factors that stimulate the regeneration of hepatocytes in patients with chronic hepatitis C. Expand
...
1
2
3
4
...