Inhibition of HCV 5′-NTR and Core Expression by a Small Hairpin RNA Delivered by a Histone Gene Carrier, HPhA

siRNA (small interfering RNA) interference represents an exciting new technology that could have therapeutic applications for the treatment of viral infections. However, a major challenge in the use of siRNA as a therapeutic agent is the development of a suitable delivery system. We demonstrated that a new non-viral transgene carrier, recombinant archaeal histone from the hyperthermophile Pyrococcus horikoshii OT3 (HPhA), can transfect short hairpin RNA (shRNA) expressing plasmids into HL-7702 cells to inhibit the expression of HCV 5'NTR and Core protein and mRNA. Plasmids Psilencirle transfected by HPhA inhibited the expression of HCV 5'-NTR and Core protein and mRNA in HL-7702 cells. The transfection efficiency of HPhA in HL-7702 cells was not affected by 10% fetal calf serum (FCS). HPhA exhibited effects of transfection without apparent toxicity, and with high affinity for DNA. This suggests that HPhA may be useful for RNAi-based gene therapy in vivo.