title: Homing endonucleases: from basics to therapeutic applications.
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.
authors.affiliation: Macromolecular Crystallography Group, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), c/Melchor Fdez. Almagro 3, 28029 Madrid, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Marcaida
authors.forename: Inés G
authors.initials: IG
authors.lastname: Muñoz
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.forename: Guillermo
authors.initials: G
authors.lastname: Montoya
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D015252:Deoxyribonucleases, Type II Site-Specific / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D005810:Multigene Family / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D004706:Endodeoxyribonucleases; C066166:AI4 protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific