Address for correspondence: Dr. M.J. Damha, Department of Chemistry, Otto Maass Chemistry Building, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 2K6; Voice: 514-398-7552; fax: 514-398-3797.
e-mail: [email protected]

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Abstract

Abstract: Antisense oligonucleotides (AON) are being developed for a wide array of therapeutic applications. Significant improvements in their serum stability, target affinity, and safety profile have been achieved with the development of chemically modified oligonucleotides. Here, we compared 2′-deoxy-2′-fluoro-β-D-arabinonucleic acid (FANA)-containing AONs with phosphorothioate oligodeoxynucleotides (PS-DNA), 2′-O-methyl-RNA/DNA chimeras and short interfering RNAs (siRNA) with respect to their target knockdown efficacy, duration of action and resistance to nuclease degradation. Results show that two different configurations of FANA/DNA chimeras (altimers and gapmers) were found to have potent antisense activity. Specific target inhibition was observed with both FANA configurations with an estimated EC₅₀ value comparable to that of an siRNA but 20-to 100-fold lower than the other commonly used AONs. Moreover, the FANA/DNA chimeras showed increased serum stability that was correlated with sustained antisense activity for up to 4 days. Taken together, these results indicate that chimeric FANA/DNA AONs are promising new tools for therapeutic gene silencing when increased potency and duration of action are required.

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Citing Literature

Volume1082, Issue1

Oligonucleotide Therapeutics: First Annual Meeting of the Oligonucleotide Therapeutics Society

October 2006

Pages 91-102

Characterization of Antisense Oligonucleotides Comprising 2′-Deoxy-2′-Fluoro-β-d-Arabinonucleic Acid (FANA)

Specificity, Potency, and Duration of Activity

Abstract

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Characterization of Antisense Oligonucleotides Comprising 2′-Deoxy-2′-Fluoro-β-d-Arabinonucleic Acid (FANA)

Specificity, Potency, and Duration of Activity

Abstract

REFERENCES

Citing Literature

References

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