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Silencing of viral RNAs by small double-stranded siDNA

Background

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 [13], HSV [4], Influenza [5], HCV, HBV, and telomerase RNA in malignant melanoma cells in mice [6]. 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 [7], inactivate HIV virus particles to prevent infections, inactivate cell-free HIV in the blood from infected individuals [8], in the vagina of mice [9], and increase survival time of retroviral-infected mice [10]. 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 [11] but with different kinetics. The method may complement existing silencing approaches.

References

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Correspondence to Karin Moelling.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Malignant Melanoma
  • Influenza
  • Malignant Melanoma Cell
  • Influenza Virus
  • Cellular mRNAs