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发表于 2003-4-14 03:19
RNA Interference Is Effective Against HBV Infection
By Brian Boyle, MD
Hepatitis B virus (HBV) infection is a global problem that infects 350 million people and is responsible for 1 million deaths per year. Options for HBV infection remain limited, although with the availability of Hepsera (adefovir) and Epivir-HBV (lamivudine), treatment options have expanded beyond interferon-based therapies.
Still, resistance to Epivir-HBV has been demonstrated and HBV resistance is likely to present a significant obstacle to long-term suppression of HBV.
In a study published in Hepatology, RNA interference (RNAi) ?a process that uses double-stranded RNA (dsRNA) to induce sequence-specific degradation of homologous messenger RNA (mRNA) ?was explored as a treatment option for HBV. To evaluate the anti-HBV therapeutic potential of RNAi, investigators from Israel designed 2 pSUPER (suppression of endogenous RNA) vectors, each of which targeted a distinct 19 nucleotide sequence in the HBV genome.
Through a series of experiments, the investigators were able to show that co-transfection of siRNA producing vectors, targeted against specific sequences in the HBV genome, resulted in a significant reduction in the corresponding HBV transcripts and proteins. This reduction appears to be highly selective and sequence-specific, with the introduction of point mutations in the target gene abrogating its action.
Importantly, specific siRNAs dramatically inhibit HBV replication, as is evident by decreasing levels of all viral replicative forms. Finally, impairing the viral core and polymerase proteins by introducing a GFP sequence into the viral genome does not alter RNAi ability to reduce the expression of viral transcripts, indicating that siRNA activity is not dependent on viral replication.
The authors conclude, 搊ur present results open a new avenue for treating HBV infection, which remains a common and serious disease.?/span>
04/11/03
Reference
A Shlomai and Y Shaul. Inhibition of Hepatitis B Virus Expression and Replication by RNA Interference. Hepatology 2003;37:764-770.
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