Elimination of hepatitis C virus RNA in infected human hepatocytes by adenovirus-mediated expression of ribozymes.
Hepatitis C virus (HCV), a positive-strand RNA virus, is the major infectious agent responsible for causing chronic hepatitis. Currently, there is no vaccine for HCV infection, and the only therapy for chronic hepatitis C is largely ineffective. To investigate new genetic approaches to the management of HCV infection, six hammerhead ribozymes directed against a conserved region of the plus strand and minus strand of the HCV genome were isolated from a ribozyme library, characterized, and expressed from recombinant adenovirus vectors. The expressed ribozymes individually or in combination were efficient at reducing or eliminating the respective plus- or minus-strand HCV RNAs expressed in cultured cells and from primary human hepatocytes obtained from chronic HCV-infected patients. This study demonstrates the potential utility of ribozyme therapy as a strategy for the treatment of hepatitis C virus infection.
Lieber
A
A
Department of Medicine, University of Washington, Seattle 98195, USA.
He
C Y
CY
Polyak
S J
SJ
Gretch
D R
DR
Barr
D
D
Kay
M A
MA
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D015870:Gene Expression; D005822:Genetic Vectors; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000473:pathology / Q000821:virology*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D011993:Recombinant Fusion Proteins
D016337:RNA, Catalytic; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins