Antiretroviral effect of a gag-RNase HI fusion gene

G. Schumann, K. Cannon, W. P. Ma, R. J. Crouch, J. D. Boeke

    Research output: Contribution to journalArticlepeer-review

    Abstract

    We have previously shown that a molecule consisting of a fusion of a Ca2+-dependent nuclease (from Staphylococcus aureus) to a retroviral coat protein specifies a potent anti-viral specific for that retrovirus. Genes specifying such fusion proteins can be delivered to virus-susceptible cells, providing an antiviral gene therapy aimed at limiting virus spread. We report here the results of experiments to vary the nuclease moiety of such fusion proteins. We found that one nuclease, Serratia marcescens nuclease, was extremely toxic to host cells and hence not likely to be useful for therapeutic purposes. A second nuclease, Escherichia coli RNase HI was found to be nontoxic and highly effective against a murine leukemia virus when it was fused to the leukemia virus coat protein. The fusion protein was enzymatically active and stably expressed, without apparent toxicity to host cells. Reduction in infectious virus output was as high as 97-99%. These studies provide a model system for the development of gene therapeutic agents aimed at combating retroviral infection in vivo.

    Original languageEnglish (US)
    Pages (from-to)593-599
    Number of pages7
    JournalGene Therapy
    Volume4
    Issue number6
    DOIs
    StatePublished - 1997

    Keywords

    • Antiviral gene therapy
    • Murine leukemia virus
    • RCAS vectors
    • RNase HI
    • Serratia nuclease

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics

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