[Antiviral effects of dual-target antisense rna: an experimental study with hepatitis B virus transgenic mice].
OBJECTIVE
To investigate the curative effects of dual-target antisense RNA targeting the X and P regions in the genome of hepatitis B virus (HBV).


METHODS
Retrovirus vector pLXSN was used to construct 4 kinds of recombinant vector plasmids expressing dual-target antisense RNA complementary to the X and P regions in the genome of HBV, namely, pLXSN-asX, pLXSN-asP, pLXSN-asXP, and pLXSN-seX. 48 HBV transgenic mice were randomly divided into 6 equal groups: pLXSN-asX group, pLXSN-asX group, pLXSN-asX group, pLXSN-asX group, and blank plasmid blank (pLXSN) group, to be injected into the caudal vein with corresponding plasmids thrice for every other day, and blank control group. Venous blood samples were collected before, 1 day and 3 days, and 2, 4, and 8 weeks after the injection to undergo detection of serum HBV DNA and HBsAg. Eight weeks later the mice were killed and immunohistochemistry was used t examine the HBsAg and HBcAg in the tissues. Pathological examination of the tissues was performed.


RESULTS
The serum HBsAg concentrations 4 and 8 weeks after injection were significantly lower than that before injection in the.pLXSN-asX and pLXSN-asXP groups (all P <0.05) with an inhibition rate of 24% and 27% respectively. In comparison with that before injection, the HBV DNA expression level 2 weeks after injection was significantly lower in the pLXSN-asX group (P < 0.05) with an inhibition rate of 58%. In comparison with that before injection, the HBV DNA expression level 8 weeks after injection was significantly lower in the pLXSN-asP group (P <0.05) with an inhibition rate of 58%. In comparison with that before injection, the HBV DNA expression level in the pLXSN-asXP group showed 2 times of significant decrease 1 week and 8 weeks after injection (both P < 0.05) with the inhibition rates of 66% and 77% respectively. HBsAg and HBcAg were expressed in liver were significantly lower in the pLXSN-asX, pLXSN-asP, and pLXSN-asXP groups than in other groups (P < 0.05). No significant abnormality was found in the tissues in all groups.


CONCLUSIONS
Dual-target antisense RNA targeting the X and P regions in the genome of HBV inhibits the replication and expression of HBV, significantly stronger than single-target antisense-RNA.
Zhao
Wei
W
Department of Infectious Disease, First Hospital of Beijing University, Beijing 100034, China.
Chen
Hong
H
Peng
Zhao-yuan
ZY
Li
Wen-gang
WG
Xi
Hong-li
HL
Xu
Xiao-yuan
XY