Efficient inhibition of hepatitis B virus replication by hepatitis delta virus ribozymes delivered by targeting retrovirus.
BACKGROUND
Hepatitis delta virus (HDV) ribozyme is an attractive molecular tool that can specifically recognize and catalyze the self-cleavage of the viral RNA phosphodiester backbone. However, a major obstacle in the medical application of the HDV ribozyme is the lack of specificity in the delivery of the ribozyme to defined target cells.


RESULTS
The objective of this study was to determine whether retroviral vectors can deliver the HDV ribozyme into the target cells and to elucidate whether HDV ribozyme plays a role in hepatitis B virus (HBV) replication. In our study, the transduction of helper-free pseudotyped retrovirus, which showed a broad host range, in human hepatoma cells was performed under 2 conditions, that is, in the presence of polymerized human serum albumin (pHSA) and in the absence of pHSA. The transduction ability in the presence of pHSA was higher than in the absence of pHSA. Moreover, HBsAg and HBeAg levels after transductions with pHSA were significantly lower than those in the absence of pHSA, thus indicating that the recombinant retrovirus had HBV-specific cleavage activity and targeted HepG2215 cells.


CONCLUSIONS
These data suggest that this system provides a new approach for targeting hepatocytes and has a great potential in gene therapy for HBV infection.
Wang
Chuan-Xi
CX
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangdong Province, PR China.
Lu
Yan-Qin
YQ
Qi
Peng
P
Chen
Long-Hua
LH
Han
Jin-Xiang
JX
D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001688:Biological Products / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D005822:Genetic Vectors; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000187:drug effects*; D003698:Hepatitis Delta Virus / Q000201:enzymology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D016337:RNA, Catalytic / Q000493:pharmacokinetics / Q000494:pharmacology*; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D001688:Biological Products; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016337:RNA, Catalytic