Site-directed genome modification: derivatives of DNA-modifying enzymes as targeting tools

C J Coates, J M Kaminski, J B Summers, D J Segal, A D Miller, Andreas Kolb

    Research output: Contribution to journalLiterature review

    34 Citations (Scopus)

    Abstract

    The modification of mammalian genomes is an important goal in gene therapy and animal transgenesis. To generate stable genetic and biochemical changes, the therapeutic genes or transgenes need to be incorporated into the host genome. Ideally, the integration of the foreign gene should occur at sites that ensure their continual expression in the absence of any unwanted side effects on cellular metabolism. In this article, we discuss the opportunities provided by natural DNA-modifying enzymes, such as transposases, recombinases and integrases, to mediate the stable integration of foreign genes into host genomes. In addition, we discuss the approaches that have been taken to improve the efficiency and to modify the site-specificity of these enzymes.

    Original languageEnglish
    Pages (from-to)407-419
    Number of pages13
    JournalTrends in Biotechnology
    Volume23
    Issue number8
    DOIs
    Publication statusPublished - Aug 2005

    Keywords

    • sleeping-beauty transposition
    • immunodeficiency-virus type-1
    • embryonic stem-cells
    • adenoassociated-virus
    • binding domain
    • in-vitro
    • transposable elements
    • TN7 transposition
    • crystal-structure
    • mammalian-cells

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