scholarly journals Specific inhibition of hepatitis C virus expression by antisense oligodeoxynucleotides. In vitro model for selection of target sequence.

1994 ◽  
Vol 269 (19) ◽  
pp. 14205-14210
Author(s):  
T. Wakita ◽  
J.R. Wands
1999 ◽  
Vol 13 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Robert G Gish

Hepatitis C virus (HCV) infects over 170 million people worldwide. While interferon is currently the most used single agent therapy, this drug may result in a sustained loss of virus from the blood in only up to 15% of patients; new options for treatment are needed. With the release of ribavirin in North America and Europe, a viral clearance rate or ‘cure’ may be attained in up to 40% of patients. Developing successful antiviral therapy that prevents or delays the development of cirrhosis, liver failure and liver cancer as well as decreasing the demand for liver transplantation are clearly identified goals. Unfortunately, there is no complete in vitro model of HCV replication or translation. Due to the lack of an animal or cell culture model of HCV infection, in vitro translation screening systems to identify inhibitors of HCV protein translation are being evaluated by a large number of biotechnology companies. With advancing computer technology, high throughput screening processes are now possible and can be joined to specific in vitro model testing systems. Along with examining some of the information known about HCV therapy and the HCV genome, the present review discusses potential targets for new therapies and identifies therapeutic agents that are nearing clinical application


2005 ◽  
Vol 42 (5) ◽  
pp. 744-751 ◽  
Author(s):  
Karim Abid ◽  
Valerio Pazienza ◽  
Andrea de Gottardi ◽  
Laura Rubbia-Brandt ◽  
Beatrice Conne ◽  
...  

2012 ◽  
Vol 56 ◽  
pp. S338
Author(s):  
S. Pisonero-Vaquero ◽  
M.V. García-Mediavilla ◽  
F. Jorquera ◽  
P.L. Majano ◽  
J. Gonzalez-Gallego ◽  
...  

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Usman Ali Ashfaq ◽  
Shaheen N Khan ◽  
Zafar Nawaz ◽  
Sheikh Riazuddin

2011 ◽  
Vol 56 (3) ◽  
pp. 1331-1341 ◽  
Author(s):  
Philip J. F. Troke ◽  
Marilyn Lewis ◽  
Paul Simpson ◽  
Katrina Gore ◽  
Jennifer Hammond ◽  
...  

ABSTRACTFilibuvir (PF-00868554) is an investigational nonnucleoside inhibitor of the hepatitis C virus (HCV) nonstructural 5B (NS5B) RNA-dependent RNA polymerase currently in development for treating chronic HCV infection. The aim of this study was to characterize the selection of filibuvir-resistant variants in HCV-infected individuals receiving filibuvir as short (3- to 10-day) monotherapy. We identified amino acid M423 as the primary site of mutation arising upon filibuvir dosing. Through bulk cloning of clinical NS5B sequences into a transient-replicon system, and supported by site-directed mutagenesis of the Con1 replicon, we confirmed that mutations M423I/T/V mediate phenotypic resistance. Selection in patients of an NS5B mutation at M423 was associated with a reduced replicative capacityin vitrorelative to the pretherapy sequence; consistent with this, reversion to wild-type M423 was observed in the majority of patients following therapy cessation. Mutations at NS5B residues R422 and M426 were detected in a small number of patients at baseline or the end of therapy and also mediate reductions in filibuvir susceptibility, suggesting these are rare but clinically relevant alternative resistance pathways. Amino acid variants at position M423 in HCV NS5B polymerase are the preferred pathway for selection of viral resistance to filibuvirin vivo.


1988 ◽  
Vol 254 (6) ◽  
pp. H1211-H1217 ◽  
Author(s):  
M. E. Schelling ◽  
C. J. Meininger ◽  
J. R. Hawker ◽  
H. J. Granger

Coronary venular endothelial cells were isolated by a bead-perfusion technique that allowed the selection of endothelial cells from venules of a specific size. Culture conditions for the microvascular cells were established. Cells grew well in supplemented Dulbecco's modified Eagle's medium. The effect of various substrata on the proliferation of the venular endothelial cells was determined. Matrigel, gelatin, and fibronectin supported high levels of proliferation. Cell shape was correlated with ability of the substratum to support cell proliferation. Cells exhibiting a broad, flattened morphology achieved high levels of proliferation. The formation of vessel meshworks by the coronary venular endothelial cells provides an in vitro model for the study of coronary angiogenesis. Confluent monolayers of these cells can be utilized to examine mechanisms of water and protein transport across coronary venules.


2017 ◽  
Vol 429 (14) ◽  
pp. 2246-2264 ◽  
Author(s):  
Bernard S. Bagaya ◽  
Meijuan Tian ◽  
Gabrielle C. Nickel ◽  
José F. Vega ◽  
Yuejin Li ◽  
...  

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