Dr. Tao, Mi-Hua 陶秘華 博士



Combinatorial RNA Interference Therapy Prevents Selection of Preexisting HBV Variants in Human Liver Chimeric Mice.

Scientific Reports, Oct 20, 2015

Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a shRNA S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy markedly reduced titers for both wild-type and T472C HBV. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients.

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