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RNA Interference inhibits hepatitis B virus of different genotypes in vitro and in vivo.

Zhang YL, Cheng T, Cai YJ, Yuan Q, Liu C, Zhang T, Xia DZ, Li RY, Yang LW, Wang YB, Yeo AE, Shih JW, Zhang J, Xia NS - BMC Microbiol. (2010)

Bottom Line: Small interfering RNA (siRNA) can be a potential new tool for HBV therapy.Given the high heterogeneity of HBV strains and the sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor against the conservative site on the HBV genome is essential to ensure a therapeutic application.No unusual cytotoxicity or off-target effects were noted.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, Fujian Province, China.

ABSTRACT

Background: Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) can be a potential new tool for HBV therapy. Given the high heterogeneity of HBV strains and the sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor against the conservative site on the HBV genome is essential to ensure a therapeutic application.

Results: Forty short hairpin RNA (shRNA) expression plasmids were constructed to target conserved regions among nine HBV genotypes. HBV 1.3-fold genome plasmids carrying various genotypes were co-transfected with shRNA plasmids into either Huh7 cells or mice. The levels of various viral markers were examined to assess the anti-HBV efficacy of siRNA. Four (B245, B376, B1581 and B1789) were found with the ability to potently inhibit HBV RNA, DNA, surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression in HBV genotypes A, B, C, D and I (a newly identified genotype) in Huh7 cells and in mice. No unusual cytotoxicity or off-target effects were noted.

Conclusions: Such siRNA suggests an alternate way of inhibiting various HBV genotypes in vitro and in vivo, promising advances in the treatment of HBV.

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Related in: MedlinePlus

Comparing the RNAi-induced silencing effect on different viral markers. Data were displayed the average antigen level of the 4 siRNAs reduced for five HBV strains. "Ex" = Extracellular and "In" = Intracellular. The Mann-Whitney test was used to assess the difference. An asterisk represents a statistical difference of P < 0.01 in comparison with the other markers (Ex HBeAg vs. Others P < 0.001, Ex HBsAg vs. In HBsAg P = 0.05, Ex HBsAg vs. In HBcAg P = 0.82, In HBsAg vs. In HBcAg P = 0.10.)
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Figure 5: Comparing the RNAi-induced silencing effect on different viral markers. Data were displayed the average antigen level of the 4 siRNAs reduced for five HBV strains. "Ex" = Extracellular and "In" = Intracellular. The Mann-Whitney test was used to assess the difference. An asterisk represents a statistical difference of P < 0.01 in comparison with the other markers (Ex HBeAg vs. Others P < 0.001, Ex HBsAg vs. In HBsAg P = 0.05, Ex HBsAg vs. In HBcAg P = 0.82, In HBsAg vs. In HBcAg P = 0.10.)

Mentions: In addition, the extracellular and intracellular antigen levels in Huh7 cells that were co-transfected with HBV and shRNA plasmids were also determined (Figure 4). In the shRNA-treated Huh7 cells, the average extracellular HBsAg expression level of all five HBV strains decreased by 1.66 ± 0.36 logs. The average intracellular HBsAg expression level decreased by 1.47 ± 0.33 logs, while the extracellular HBeAg levels decreased by 1.04 ± 0.23 logs, and the intracellular HBcAg levels by 1.71 ± 0.49 logs. The effect of the siRNA treatment on HBeAg levels was weaker than that on the HBsAg or HBcAg levels (P < 0.001, Figure 5).


RNA Interference inhibits hepatitis B virus of different genotypes in vitro and in vivo.

Zhang YL, Cheng T, Cai YJ, Yuan Q, Liu C, Zhang T, Xia DZ, Li RY, Yang LW, Wang YB, Yeo AE, Shih JW, Zhang J, Xia NS - BMC Microbiol. (2010)

Comparing the RNAi-induced silencing effect on different viral markers. Data were displayed the average antigen level of the 4 siRNAs reduced for five HBV strains. "Ex" = Extracellular and "In" = Intracellular. The Mann-Whitney test was used to assess the difference. An asterisk represents a statistical difference of P < 0.01 in comparison with the other markers (Ex HBeAg vs. Others P < 0.001, Ex HBsAg vs. In HBsAg P = 0.05, Ex HBsAg vs. In HBcAg P = 0.82, In HBsAg vs. In HBcAg P = 0.10.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927532&req=5

Figure 5: Comparing the RNAi-induced silencing effect on different viral markers. Data were displayed the average antigen level of the 4 siRNAs reduced for five HBV strains. "Ex" = Extracellular and "In" = Intracellular. The Mann-Whitney test was used to assess the difference. An asterisk represents a statistical difference of P < 0.01 in comparison with the other markers (Ex HBeAg vs. Others P < 0.001, Ex HBsAg vs. In HBsAg P = 0.05, Ex HBsAg vs. In HBcAg P = 0.82, In HBsAg vs. In HBcAg P = 0.10.)
Mentions: In addition, the extracellular and intracellular antigen levels in Huh7 cells that were co-transfected with HBV and shRNA plasmids were also determined (Figure 4). In the shRNA-treated Huh7 cells, the average extracellular HBsAg expression level of all five HBV strains decreased by 1.66 ± 0.36 logs. The average intracellular HBsAg expression level decreased by 1.47 ± 0.33 logs, while the extracellular HBeAg levels decreased by 1.04 ± 0.23 logs, and the intracellular HBcAg levels by 1.71 ± 0.49 logs. The effect of the siRNA treatment on HBeAg levels was weaker than that on the HBsAg or HBcAg levels (P < 0.001, Figure 5).

Bottom Line: Small interfering RNA (siRNA) can be a potential new tool for HBV therapy.Given the high heterogeneity of HBV strains and the sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor against the conservative site on the HBV genome is essential to ensure a therapeutic application.No unusual cytotoxicity or off-target effects were noted.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, Fujian Province, China.

ABSTRACT

Background: Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) can be a potential new tool for HBV therapy. Given the high heterogeneity of HBV strains and the sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor against the conservative site on the HBV genome is essential to ensure a therapeutic application.

Results: Forty short hairpin RNA (shRNA) expression plasmids were constructed to target conserved regions among nine HBV genotypes. HBV 1.3-fold genome plasmids carrying various genotypes were co-transfected with shRNA plasmids into either Huh7 cells or mice. The levels of various viral markers were examined to assess the anti-HBV efficacy of siRNA. Four (B245, B376, B1581 and B1789) were found with the ability to potently inhibit HBV RNA, DNA, surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression in HBV genotypes A, B, C, D and I (a newly identified genotype) in Huh7 cells and in mice. No unusual cytotoxicity or off-target effects were noted.

Conclusions: Such siRNA suggests an alternate way of inhibiting various HBV genotypes in vitro and in vivo, promising advances in the treatment of HBV.

Show MeSH
Related in: MedlinePlus