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Homing endonucleases: from basics to therapeutic applications

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Abstract

Homing endonucleases (HE) are double-stranded DNAses that target large recognition sites (12–40 bp). HE-encoding sequences are usually embedded in either introns or inteins. Their recognition sites are extremely rare, with none or only a few of these sites present in a mammalian-sized genome. However, these enzymes, unlike standard restriction endonucleases, tolerate some sequence degeneracy within their recognition sequence. Several members of this enzyme family have been used as templates to engineer tools to cleave DNA sequences that differ from their original wild-type targets. These custom HEs can be used to stimulate double-strand break homologous recombination in cells, to induce the repair of defective genes with very low toxicity levels. The use of tailored HEs opens up new possibilities for gene therapy in patients with monogenic diseases that can be treated ex vivo. This review provides an overview of recent advances in this field.

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Acknowledgments

This work was supported European Union MEGATOOLS (LSHG-CT-2006-037226), the Ministerio de Ciencia e Inovación (MICINN) Grant BFU2007-30703-E and BFU2008-01344 to G.M., and the ETORTEK-2008 programme, at the Structural Biology Unit of CIC bioGUNE. M.J.M. holds a Juan de la Cierva contract from the Spanish MICINN.

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  1. Macromolecular Crystallography Group, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), c/Melchor Fdez. Almagro 3, 28029, Madrid, Spain

    Maria J. Marcaida, Inés G. Muñoz, Jesús Prieto & Guillermo Montoya

  2. Ikerbasque Professor Structural Biology Unit, CIC bioGUNE, Parque Tecnológico de Vizcaya, 48160, Derio, Spain

    Francisco J. Blanco

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  1. Maria J. Marcaida
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  2. Inés G. Muñoz
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  3. Francisco J. Blanco
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  4. Jesús Prieto
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  5. Guillermo Montoya
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Correspondence to Jesús Prieto or Guillermo Montoya.

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Marcaida, M.J., Muñoz, I.G., Blanco, F.J. et al. Homing endonucleases: from basics to therapeutic applications. Cell. Mol. Life Sci. 67, 727–748 (2010). https://doi.org/10.1007/s00018-009-0188-y

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  • DOI: https://doi.org/10.1007/s00018-009-0188-y

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