No abstract

RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAibased therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and uniform transduction of the whole infected hepatocytes. To increase the in vivo transfection efficiency in liver, we used a double-stranded adenoassociated virus 8-pseudotyped vector (dsAAV2/8) to deliver shRNA. HBV transgenic mice were used as an animal model to evaluate the inhibition effects of the RNAi-based gene therapy. A single administration of dsAAV2/8 vector, carrying HBV-specific shRNA, effectively suppressed the steady level of HBV protein, mRNA and replicative DNA in liver of HBV transgenic mice, leading to up to 2-3 log 10 decrease in HBV load in the circulation. Significant HBV suppression sustained for at least 120 days after vector administration. The therapeutic effect of shRNA was target sequence dependent and did not involve activation of interferon. These results underscore the potential for developing RNAi-based therapy by dsAAV2/8 vector to treat HBV chronic infection, and possibly other persistent liver infections as well.

No abstract

Pharmacogenomics aims to unravel the way that human genetic variation affects drug efficacy and toxicity. Genome-wide association studies and candidate gene findings suggest that genetic approaches may help choose the most appropriate drug and dosage while preventing adverse drug reactions (ADRs). Pain is an unpleasant feeling that usually results from tissue damage. The management of different types of pain (acute, chronic, inflammatory, neuropathic, or cancer) is challenging. Currently, drug intervention is the first-line therapy for resolving pain. However, differences in drug efficacy between individuals are common with pain medications. Moreover, some patients experience ADRs after being treated with specific pain drugs. This review discusses the use of drugs for pain management in the context of the recent pharmacogenomic studies on ADRs and drug efficacy.