In:
Journal of General Virology, Microbiology Society, Vol. 86, No. 12 ( 2005-12-01), p. 3227-3234
Abstract:
The strategy of RNA interference (RNAi)-based gene silencing has been suggested to have great potential in treating viral diseases. It provides new hope of being able to complement the limited therapeutic options currently available for chronic hepatitis B virus (HBV) infection. To advance such a strategy towards clinical use, the effects of various parameters on the anti-HBV efficiency of RNAi need to be well-defined. In this study, the efficacy and pharmacodynamic properties of different RNAi target sequences and constructs were examined. Several sequences were found to be effective in cell and animal models, achieving inhibition rates of approximately 80–90 %. Methyl-modified small interfering RNA (siRNA) molecules were found to be more stable inside cells than natural siRNA molecules and offered longer-lasting inhibitory effects. Both were effective at rather low doses (an equimolar ratio with HBV preS2–S protein expression vector). Plasmid DNA vectors were less dose-responsive, but their effectiveness in vivo lasted longer, for approximately 1 month. By analysing these different parameters and their possible mechanisms, some important issues in RNAi therapeutics that should assist the future development of clinical applications have been addressed.
Type of Medium:
Online Resource
ISSN:
0022-1317
,
1465-2099
DOI:
10.1099/vir.0.81171-0
Language:
English
Publisher:
Microbiology Society
Publication Date:
2005
detail.hit.zdb_id:
2007065-2
SSG:
12
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