Inhibition of viral transcription using designed zinc finger proteins.
Currently available therapeutics for hepatitis B virus (HBV) infection have limited effectiveness in patients and often do not clear HBV from the liver due to the persistence of the stable, double-stranded (ds) DNA genome of HBV. By designing zinc finger proteins (ZFPs) to bind the dsDNA genome of a model virus, duck HBV (DHBV), we were able to inhibit viral transcription, and subsequently, viral protein and progeny production. This inhibition is likely due to competition for DNA binding sites between the ZFPs and transcription factors, and interference with read-through transcription by RNA polymerase across the ZFP-binding region. Taking into account some design considerations, this method of inhibiting viral transcription can be applied to other viral infections where viral dsDNA occurs.
Hoeksema
Kimberley A
KA
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.
Tyrrell
D Lorne J
DL
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D015611:Hepatitis B Virus, Duck / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D016335:Zinc Fingers / Q000235:genetics*
D004279:DNA, Viral; D004268:DNA-Binding Proteins