destruction hiv viral rna by sidna triggering rnase h

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POSTER PRESENTATION Open Access Destruction HIV viral RNA by siDNA triggering RNAse H Karin Moelling From 16 th International Symposium on HIV and Emerging Infectious Diseases Marseille, France. 24-26 March 2010 Background We are developing an alternative approach to siRNA, which may be designated as siDNA, small interfering DNA, by using hairpin-loop-structured DNA oligodeox- ynucleotides (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. Methods We selected ODNs against various viral and mRNAs of HIV, HSV, Influenza, HCV, HBV, and the terminal repeat of telomerases in malignant melanomas 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. Results The ODNs were most effective in HIV. We are able to induce HIV suicide and 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 tumor formation in mice 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 and enhance uptake Discussion The dsODNS are often superior to single-stranded anti- sense DNA and resemble the effects of siRNAs but with different kinetics. The method may complement existing silencing approaches. Published: 11 May 2010 doi:10.1186/1742-4690-7-S1-P95 Cite this article as: Moelling: Destruction HIV viral RNA by siDNA triggering RNAse H. Retrovirology 2010 7(Suppl 1):P95. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Correspondence: [email protected] University of Zurich, Zurich, Switzerland Moelling Retrovirology 2010, 7(Suppl 1):P95 http://www.retrovirology.com/content/7/S1/P95 © 2010 Moelling; licensee BioMed Central Ltd.

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POSTER PRESENTATION Open Access

Destruction HIV viral RNA by siDNA triggeringRNAse HKarin Moelling

From 16th International Symposium on HIV and Emerging Infectious DiseasesMarseille, France. 24-26 March 2010

BackgroundWe are developing an alternative approach to siRNA,which may be designated as siDNA, small interferingDNA, by using hairpin-loop-structured DNA oligodeox-ynucleotides (ODN), targeted to viral or cellularmRNAs. ODNs activate the viral RNase H in retroviralparticles and cellular RNases H inside the cell. AlsoAgo2 may play a role. Other inhibitory mechanismssuch as translational arrest may contribute.

MethodsWe selected ODNs against various viral and mRNAs ofHIV, HSV, Influenza, HCV, HBV, and the terminalrepeat of telomerases in malignant melanomas in mice.The ODNs were applied with or without carriers.Furthermore their effects were directly compared tothose of single-stranded antisense DNAs and siRNAs toallow comparison of the various efficiencies.

ResultsThe ODNs were most effective in HIV. We are able toinduce HIV suicide and inactivate HIV virus particles toprevent infections, inactivate cell-free HIV in the bloodfrom infected individuals, in the vagina of mice, andincrease survival time of retroviral-infected mice. Alsoinfluenza virus replication was reduced in the lungs of amouse model. Furthermore we could reduce malignantmelanoma-formation tumor formation in mice targetingthe 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 Gtracts, which may form higher-ordered structures andenhance uptake

DiscussionThe dsODNS are often superior to single-stranded anti-sense DNA and resemble the effects of siRNAs but withdifferent kinetics. The method may complement existingsilencing approaches.

Published: 11 May 2010

doi:10.1186/1742-4690-7-S1-P95Cite this article as: Moelling: Destruction HIV viral RNA by siDNAtriggering RNAse H. Retrovirology 2010 7(Suppl 1):P95.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

Correspondence: [email protected] of Zurich, Zurich, Switzerland

Moelling Retrovirology 2010, 7(Suppl 1):P95http://www.retrovirology.com/content/7/S1/P95

© 2010 Moelling; licensee BioMed Central Ltd.