The inhibitory efficacy of these shRNAs (B245, B376, B1581 and B1789) however, varies significantly against the various genotypes for different viral markers in different models (Figure 3, 4, 5 and 6). Such differences click here in efficiency may be due to differences in the mRNA’s secondary structure or the target site accessibility [26]. B245 was the most effective of the four candidates. It should be noted that both the cell-transfection model and hydrodynamic injection model more closely resemble an acute model of a HBV infection. This is a potential limitation in this study, as most individuals who need anti-HBV therapy are

Metabolism inhibitor chronically infected. Compared to the HBV transgenic mouse models and stably transfected cell lines, the MM-102 supplier former are more

flexible and convenient in evaluating the efficacy of shRNAs as a way to inhibit various HBV strains. Nevertheless, the effective shRNA candidates should be studied further in different models. Because HBV contains overlapping open reading frames (ORFs) and all four HBV transcripts overlap in their 3′ terminals, a single siRNA targeting multiple areas could be designed to maximize inhibitory potency [23]. The siRNAs targeting C ORF, such as B2389~B2397, presented in Table 1, show activity only against the 3.5 kb pregenomic RNA, but are unlikely to show any activity against the other three transcripts (Figure 1). Meanwhile, all four siRNAs demonstrated

more silencing activity with regards to HBsAg Dichloromethane dehalogenase expression than HBeAg expression for various genotypes in the cell cultures and mice. The targets on both however were the same in the HBV transcripts for the two proteins (Figure 4 and Figure 5), which was also observed in a previous study [23]. HBcAg, a viral capsid correlated with viral replication [27, 28], was silenced as effectively as HBsAg, but HBeAg was not (Figure 4). The registered agents currently available for the treatment of HBV infections, such as interferon and nucleoside analogues, can dramatically decrease HBV DNA levels and induce particular HBeAg loss, but will rarely cause HBsAg loss in chronic hepatitis B patients [29–32]. RNA interference, on the other hand, can theoretically be directed to cleave any target RNA, providing a novel methodology for anti-HBV therapy [33]. In the present study, and supported by other studies [13, 34, 35], using RNAi as an inhibitor for HBV effectively reduces viral antigen levels, including HBsAg. It can be speculated that RNAi-treatments may offer complementary effects for current anti-HBV therapy. However, the final application of RNAi-based anti-HBV drugs depends on the development of effective and safe RNAi delivery systems. Conclusions In summary, four candidate shRNA plasmids significantly inhibited HBV genotypes A, B, C, D and I in vitro and in vivo.