Viruses

SiDNA-mediated gene silencing by hairpin loop-structured oligodeoxynucleotides (ODN) was applied to interfere with replication of viruses and expression of oncogenes to develop interventions against infectious diseases and cancer. Viruses successfully treated were HIV, Influenza, and HSV. Further studies with HBV, HCV, BKV are preliminary and might be continued in collaborations. Oncogenes targeted were Raf and telomerase known to be overexpressed in various cancers.

Most important recent papers for immediate reading

  • Kwok, T., Helfer, H., Alam, M.I., Heinrich, J., Pavlovic, J., and Moelling, K. (2009). Inhibition of influenza A virus replication by short double-stranded oligodeoxynucleotides. Arch Virol 154, 109-114. – Kwok 2009.pdf
  • Falkenhagen, A., Heinrich, J., and Moelling, K. (2009). Short hairpin-loop-structured Oligodeoxynucleotides reduce HSV-1 Replication. Virology Journal 6,43, doi: 10.1186/ 1743-422X-6-43.Falkenhagen 2009.pdf
  • Noreen, F., Heinrich, J., Moelling, K. (2009). Anti-tumor activity of small double-stranded oligodeoxynucleotides targeting telomerase RNA in malignant melanoma cells. Oligonucleotides 19:2, 169-178.Noreen 2009.pdf
  • Hofmann, M.H., Heinrich, J., Radziwil, G. and Moelling K. (2009) A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells. Mol Cancer Res 7, 1635-44. – Hofmann 2009.pdf

Publications about ODN-mediated silencing of viruses and oncogenes

  1. Hansen, J., Schulze, T. and Moelling, K. (1987). RNase H activity associated with bacterially expressed reverse transcriptase of human T-cell lymphotropic virus III/lymphadenopathy-associated virus. J Biol Chem. 262 (26): 12393-12396.
  2. Hansen, J., Schulze, T., Mellert, W. and Moelling, K. (1988). Identification and characterization of HIV-specific RNase H by monoclonal antibody. EMBO J. 7(1): 239–243.
  3. Bazin, H., Chattopadhyaya, J., Datema, R., Ericson A.C., Gilljam, G., Johansson, N.G., Hansen, J., Koshida, R., Moelling, K., Oberg, B., Remaud, G., Stening, G., Vrang L., Wahren, B. and Cheng, J. (1989) An analysis of the inhibition of replication of HIV and MULV by some 3’-blocked pyrimidine analogs. Biochem Pharmacol. 38(1):109-119.
  4. Moelling, K., Schulze, T. and Diringer, H. (1989). Inhibition of human immunodeficiency virus type 1 RNase H by sulfated polyanions. J Virol. 63(12): 5489-5491.
  5. Woehrl, B.M., Moelling, K. (1990) Interaction of HIV-1 ribonuclease H with polypurine tract containing RNA-DNA hybrids. Biochemistry 29 (44):10141-7.
  6. Woehrl B.M., Volkmann, S. and Moelling, K. (1991) Mutations of a conserved residue within HIV-1 ribonuclease H affect its exo- and endonuclease activities. J. Mol. Biol. 220 (3): 801-818
  7. Tisdale, M., Schulze, T., Larder, B.A., Moelling, K. (1991) Mutations within the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase abolish virus infectivity. J Gen Virol. 72 ( Pt 1): 59-66.
  8. Volkmann, S., Dannull, J., Moelling, K. (1993) The polypurine tract, PPT, of HIV as target for antisense and triple-helix-forming oligonucleotides. Biochimie 75 : 71-78.
  9. Volkmann, S., Woehrl, B.M., Tisdale, M. and Moelling, K. (1993). Enzymatic analysis of two HIV-1 reverse transcriptase mutants with mutations in carboxyl-terminal amino acid residues conserved among retroviral ribonucleases H. J. Biol. Chem. 268:4, 2674-2683.
  10. Volkmann, S., Jendis, J., Frauendorf, A. and Moelling, K. (1995) Inhibition of HIV-1 reverse transcription by triple-helix forming oligonucleotides with viral RNA. Nucleic Acids Res. 23(7): 1204–1212.
  11. Jendis, J., Strack, B., Volkmann, S., Böni, J. and Moelling, K. (1996) Inhibition of Replication of Fresh HIV Type 1 Patient Isolates by a Polypurine Tract-Specific Self-Complementary Oligodeoxynucleotide. AIDS Res Hum Retroviruses 12 (12):1161-8.
  12. Schmalzbauer, E., Strack, B., Dannull, J., Guehmann S. and Moelling, K. (1996) Mutations of basic amino acids of NCp7 of human immunodeficiency virus type 1 affect RNA binding in vitro. J. Virol. 70 (2): 771-777.
  13. Jendis, J., Strack, B. and Moelling, K. (1998) Inhibition of replication of drug-resistant HIV type 1 isolates by polypurine tract-specific oligodeoxynucleotide TFO A. AIDS Res Hum Retroviruses. 14 (11): 999-1005.
  14. Bachmann, A.S., Surovoy, A., Jung, G. and Moelling, K. (1998) Integrin receptor-targeted transfer peptides for efficient delivery of antisense oligodeoxynucleotides. J Mol Med. 76 (2): 126-3
  15. Matskevich, A.A., Ziogas, A., Heinrich, J., Quast, S.A. and Moelling, K. (2006) Short partially double-stranded oligodeoxynucleotide induces reverse transcriptase/RNase H-mediated cleavage of HIV RNA and contributes to abrogation of infectivity of virions. AIDS Research Hum Retroviruses 22(12):1220-1230.
  16. Moelling, K., Abels, S., Jendis, J., Matskevich, A., Heinrich, J. (2006) Silencing of HIV by hairpin-loop-structured DNA oligonucleotide. FEBS Letters 580: 3545–3550.
  17. Moelling, K., Matskevich, A. and Jung, J.-S. (2007). Relationship between Retroviral Replication and RNA Interference Machineries. Cold Spring Harbor Symposia on Quantitative Biology, Volume LXXI. © 2007 Cold Spring Harbor Laboratory Press 978-087969817-1 1.
  18. Matzen, K., Elzaouk, L., Matskevich, A.A., Nitzsche, A., Heinrich, J. and Moelling, K. (2007). RNase H-mediated retrovirus destruction in vivo triggered by oligodeoxynucleotides. Nature Biotechnology 25: 669-674. [Matzen 2007.pdf]
  19. Johnson, W.E. (Comment, 2007) Assisted suicide for retroviruses. Antisense oligonucleotides activate the self-destruction of retroviruses in vivo. Nature Biotechnology 25, 643 – 644 (2007) – Comment Matzen 2007.pdf
  20. Matskevich, A.A., and Moelling, K. (2008). Stimuli-dependent cleavage of Dicer during apoptosis. Biochem J 412, 527-534.
  21. Kwok, T., Helfer, H., Alam, M.I., Heinrich, J., Pavlovic, J., and Moelling, K. (2009). Inhibition of influenza A virus replication by short double-stranded oligodeoxynucleotides. Arch Virol 154, 109-114.Kwok 2009.pdf
  22. Heinrich, J., Mathur, S., Matskevich, A.A., and Moelling, K. (2009). Oligonucleotide-mediated retroviral RNase H activation leads to reduced HIV-1 titer in patient-derived plasma. AIDS 23, 213-221. – Heinrich 2009.pdf
  23. Wainberg, M.A. (Comment, 2009) New findings on blockage of HIV-1 RNase H activity. AIDS 2009, 23 (2): 223–224. – Comment Heinrich 2009.pdf
  24. Wittmer-Elzaouk, L., Jung-Shiu, J., Heinrich, J., and Moelling, K. (2009). Retroviral self-inactivation in the mouse vagina induced by short DNA. Antiviral Res 82, 22-28.
  25. Falkenhagen, A., Heinrich, J., and Moelling, K. (2009). Short hairpin-loop-structured Oligodeoxynucleotides reduce HSV-1 Replication. Virology Journal 6,43, doi: 10.1186/ 1743-422X-6-43.Falkenhagen 2009.pdf
  26. Noreen, F., Heinrich, J., Moelling, K. (2009). Anti-tumor activity of small double-stranded oligodeoxynucleotides targeting telomerase RNA in malignant melanoma cells. Oligonucleotides 19:2, 169-178. – Noreen 2009.pdf
  27. Kwok, T., Heinrich, J., Jung-Shiu, J., Meier, M.G., Mathur, S., and Moelling, K. (2009). Reduction of gene expression by a hairpin-loop structured oligodeoxynucleotide: alternative to siRNA and antisense. Biochim Biophys. Acta 1790: 1170-1178.
  28. Hofmann, M.H., Heinrich, J., Radziwil, G. and Moelling K. (2009) A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells. Mol Cancer Res 7, 1635-44.  – Hofmann 2009.pdf
  29. Heinrich, J., Schols, D. and Moelling, K. (2009). Inhibition of HIV-1 by hairpin-loop-structured oligodeoxynucleotide in huPBL-SCID mice (submitted)