Reduction in intracellular HCV RNA and virus protein expression in human hepatoma cells following treatment with 2'-O-methyl-modified anti-core deoxyribozyme.
HCV RNA is gaining greater consideration as a principal target for newer HCV antivirals because its destruction has the potential of eliminating the virus. These newer antivirals include deoxyribozymes (Dz), which are small single-stranded DNA molecules that cleave homologous RNA targets. Using a liver cell model containing functional genomic-length HCV-1b RNA we tested whether 2'-O-methyl-modified Dz, designed to recognize a highly-conserved RNA sequence located within the core-E1 coding region, could recognize and cleave its target sequence in the structural context of a functional HCV RNA molecule. Dz858-4-OMe contains four 2'-O-methyl nucleotide derivatives consecutively located on the distal ends of its two annealing arms. Intracellular HCV RNA, core protein and HCV antigen expression were reduced by 63%, 87% and 84%, respectively, when HCV RNA was challenged 6 h post-transfection with Dz858-4-OMe. The observed reduction of intracellular HCV RNA and protein by Dz858-4-OMe suggests that it may constitute an attractive HCV antiviral.
Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Qc, Canada.
Janie B
JB
Trepanier
Jerome E
JE
Tanner
Caroline
C
Alfieri
D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology; D021881:DNA, Catalytic / Q000235:genetics / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D012367:RNA, Viral / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000187:drug effects* / Q000378:metabolism
D021881:DNA, Catalytic; D012367:RNA, Viral; D014764:Viral Proteins