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In vivo site-directed mutagenesis of the factor IX gene by chimeric RNA/DNA oligonucleotides

Nature Medicine volume 4, pages 285–290 (1998)Cite this article

Abstract

A chimeric RNA/DNA oligonucleotide was constructed to induce a sequence mutation in the rat factor IX gene, resulting in prolonged coagulation. Oligonucleotides were targeted to hepato-cytes in cell culture or in vivo by intravenous injection. Nucleotide conversion was both site-specific and dose-dependent. The mutated gene was associated in vivo with significantly reduced factor IX coagulant activity and a marked prolongation of the activated partial thromboplastin time. The results demonstrate that single base-pair alterations can be introduced in hepatocytes in situ by RNA/DNA oligonucleotides, suggesting a potentially powerful strategy for hepatic gene repair without the use of viral vectors.

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Authors and Affiliations

  1. Department of Medicine, University of Minnesota Medical School, 420 Delaware Street, SE, Minneapolis, Minnesota, 55455, USA

    Betsy T. Kren, Paramita Bandyopadhyay & Clifford J. Steer

  2. Department of Cell Biology and Neuroanatomy, University of Minnesota Medical School, 420 Delaware Street, SE, Minneapolis, Minnesota, 55455, USA

    Clifford J. Steer

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  1. Betsy T. Kren
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  2. Paramita Bandyopadhyay
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  3. Clifford J. Steer
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Kren, B., Bandyopadhyay, P. & Steer, C. In vivo site-directed mutagenesis of the factor IX gene by chimeric RNA/DNA oligonucleotides. Nat Med 4, 285–290 (1998). https://doi.org/10.1038/nm0398-285

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