In vivo site-directed mutagenesis of the factor IX gene by chimetic RND/DNA oligonucleotides

Betsy T. Kren, Paramtta Banoyopaohyay, Clifford J Steer

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

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 hepatocytes 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.

Original languageEnglish (US)
Pages (from-to)285-290
Number of pages6
JournalNature Medicine
Volume4
Issue number3
DOIs
StatePublished - 1998

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