tailieunhanh - Báo cáo y học: "Identification of an effective siRNA target site and functional regulatory elements, within the hepatitis B virus posttranscriptional regulatory element"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Identification of an effective siRNA target site and functional regulatory elements, within the hepatitis B virus posttranscriptional regulatory element | Panjaworayan et al. Virology Journal 2010 7 216 http content 7 1 216 VIROLOGY JOURNAL RESEARCH Open Access Identification of an effective siRNA target site and functional regulatory elements within the hepatitis B virus posttranscriptional regulatory element Nattanan Panjaworayan1 Sunchai Payungporn2 Yong Poovorawan3 Chris M Brown4 Abstract Background Infection with hepatitis B virus HBV is major public health concern. The limitations of available antiviral drugs require development of novel approaches to inhibit HBV replication. This study was conducted to identify functional elements and new siRNA target sites within the highly conserved regions of the 533 base post-transcriptional regulatory element PRE of HBV RNAs. Results Computational analysis of the PRE sequence revealed several conserved regulatory elements that are predicted to form local secondary structures some of these within known regulatory regions. A deletion analysis showed that sub-elements of the PRE have different effects on the reporter activity suggesting that the PRE contains multiple regulatory elements. Conserved siRNA targets at nucleotide position 1317-1337 and 1329-1349 were predicted. Although the siRNA at the position 1329-1349 had no effect on the expression of reporter gene the siRNA target site at the position 1317-1337 was observed to significantly decrease expression of the reporter protein. This siRNA also specifically reduced the level of cccDNA in transiently HBV infected cells. Conclusion The HBV PRE is likely to contain multiple regulatory elements. A conserved target within this region at 1317-1337 is an effective siRNA target. Introduction Hepatitis B virus HBV infection is a major cause of hepatocellular carcinoma and liver cirrhosis worldwide 1 . HBV vaccination can prevent new infections but effective antiviral drugs are required for the large number of HBV infected people. Current licensed therapies such as interferon-a lamivudine and adefovir .