Silencing of viral RNAs by small double-stranded siDNA
© Moelling et al; licensee BioMed Central Ltd. 2009
Published: 24 September 2009
We are developing an alternative approach to siRNA, which may be designated as siDNA, small interfering DNA, by using hairpin-loop-structured DNA oligodeoxynucleotides (ODN), targeted to viral or cellular mRNAs. ODNs activate the viral RNase H in retroviral particles and cellular RNases H inside the cell. Also Ago2 may play a role. Other inhibitory mechanisms such as translational arrest may contribute.
We selected ODNs against various viral and mRNAs of HIV [1–3], HSV , Influenza , HCV, HBV, and telomerase RNA in malignant melanoma cells in mice . The ODNs were applied with or without carriers. Furthermore their effects were directly compared to those of single-stranded antisense DNAs and siRNAs to allow comparison of the various efficiencies. The ODNs were most effective in HIV. We are able to induce HIV suicide , inactivate HIV virus particles to prevent infections, inactivate cell-free HIV in the blood from infected individuals , in the vagina of mice , and increase survival time of retroviral-infected mice . Also influenza virus replication was reduced in the lungs of a mouse model. Furthermore we could reduce malignant melanoma-formation targeting the telomerase. The effects are sequence- and dose-dependent, but the optimal algorithm is not yet known. We are analyzing whether there is a preference for G tracts, which may form higher-ordered structures. The dsODNs are often superior to single-stranded antisense DNA and resemble the effects of siRNAs  but with different kinetics. The method may complement existing silencing approaches.
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