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RNase H-independent antisense activity of oligonucleotide N3 '--> P5' phosphoramidates

Lookup NU author(s): Professor Olaf Heidenreich



Oligonucleotide N3'-->P5'phosphoramidates are a new and promising class of antisense agents. Here we report biological properties of phosphoramidate oligonucleotides targeted against the human T cell leukemia virus type-I Tax protein, the major transcriptional transactivator of this human retrovirus. Isosequential phosphorothioate oligodeoxynucleotides and uniformly modified and chimeric phosphoramidate oligodeoxynucleotides containing six central phosphodiester linkages are all quite stable in cell nuclei. The uniformly modified anti-tax phosphoramidate oligodeoxynucleotide does not activate nuclear RNase H, as was shown by RNase protection assay. In contrast, the chimeric phosphoramidate-phosphodiester oligodeoxynucleotide is an efficient activator of RNase H. The presence of one or two mismatched nucleotides in the phosphodiester portion of oligonucleotides affected this activation only negligibly. When introduced into tax-transformed fibroblasts ex vivo, only the uniformly modified anti-tax phosphoramidate oligodeoxynucleotide caused a sequence-dependent reduction in the Tax protein level. Neither the chimeric phosphoramidate nor the phosphorothioate oligodeoxynucleotides significantly reduced tax expression under similar experimental conditions.

Publication metadata

Author(s): Heidenreich O, Gryaznov S, Nerenberg M

Publication type: Article

Publication status: Published

Journal: Nucleic Acids Research

Year: 1997

Volume: 25

Issue: 4

Pages: 776-780

Date deposited: 17/02/2012

ISSN (print): 0305-1048

ISSN (electronic): 1362-4954


DOI: 10.1093/nar/25.4.776


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