Benitec Biopharma Ltd (BNTC)

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Nature Journal discussing shrna role in HBV treatment. Courtesy of Drafter on Hot Copper website.


http://www.nature.com/articles/srep15259
this paper just up on nature journal discussing possible cure for HBV using multi-shRNA vector delivery, on the back of their mice study. It includes Suhy's 2012 paper as a reference (40). Authors out of Taiwan, US, and China institutes.

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. ..
..In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients.

In this study, we used two AAV vectors each expressing a different shRNA for the combinatorial therapy. For convenience, one can simultaneously express multiple shRNAs in a single viral vector by combining multiple shRNA-expression cassettes containing the same or different promoters23,40. Alternatively, one can also apply long hairpin RNAs25 or polycistronic microRNAs41 to generate multiple siRNAs in a single cell. These novel delivery vectors, in particular the one with the microRNA backbone, may further improve the safety profiles in vivo by reducing siRNA transcription but still maintaining their silencing activity. In this regard, the combinatorial use of a multiple shRNA-delivery vector and the highly potent shRNAs identified in this study might provide a potential cure for, or long term management of, chronic HBV infection.