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.

We have utilized a recombinant adeno-associated viral (AAV)

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A statistical approach was developed to investigate the effects of pressure, temperature, mixing speed and solid concentration on kLu for gaseous hydrogen, ethylene, and propylene in liquid n-hexane containing solid polypropylene powder in a 4-litre agitated reactor. The solubilities of the gases appeared to follow Henry's Law. Statistical correlations to predict kLu were proposed and response surfaces were constructed. kLu values appeared to reach a maximum around 15 mass% and sharply decrease above 30 mass%. The effects of pressure and temperature on kLu were found to depend on the gas-liquid system and operating conditions used.On a m i s au point une mtthode statistique pour ttudier les effets de la pression, de la temphahue, de la vitesse de mtlange et de la concentration de solides sur kLu pour de I'hydrogkne, de I'ethylkne et du propylkne gazeux dans du n-hexane contenant de la poudre de polypropyltne solide dans un rkacteur agitk de 4 litres. Il semble que les solubilitks des gaz suivent la loi d'Henry. On propose des corrtlations statistiques d i n de pr6dire k,a, et des surfaces de reponse sont construites. Les valeurs de kLu semblent atteindre un maximum autour de 15% en masse et diminuent considerablement autour de 30% en masse. On a trouvt que les effets de la pression et de la temp6rature sur kLa dependaient du syst&me gaz-liquide et des conditions de fonctionnement utilisks.