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Illegitimate DNA integration in mammalian cells

Gene Therapy volume 10, pages 1791–1799 (2003)Cite this article

Abstract

Foreign DNA integration is one of the most widely exploited cellular processes in molecular biology. Its technical use permits us to alter a cellular genome by incorporating a fragment of foreign DNA into the chromosomal DNA. This process employs the cell's own endogenous DNA modification and repair machinery. Two main classes of integration mechanisms exist: those that draw on sequence similarity between the foreign and genomic sequences to carry out homology-directed modifications, and the nonhomologous or ‘illegitimate’ insertion of foreign DNA into the genome. Gene therapy procedures can result in illegitimate integration of introduced sequences and thus pose a risk of unforeseeable genomic alterations. The choice of insertion site, the degree to which the foreign DNA and endogenous locus are modified before or during integration, and the resulting impact on structure, expression, and stability of the genome are all factors of illegitimate DNA integration that must be considered, in particular when designing genetic therapies.

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  1. Programme de Biologie Moléculaire, Université de Montréal, Montréal, Canada

    H Würtele

  2. Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec, Canada

    K C E Little & P Chartrand

  3. Centre Hospitalier de l'Université de Montréal and Département de Pathologie et de Biologie Cellulaire, Université de Montréal, Montréal, Québec, Canada

    P Chartrand

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Würtele, H., Little, K. & Chartrand, P. Illegitimate DNA integration in mammalian cells. Gene Ther 10, 1791–1799 (2003). https://doi.org/10.1038/sj.gt.3302074

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