Gene targeting is a technique to introduce genetic change into one or morespecific locations in the genome of a cell. For example, gene targeting canintroduce genetic change by modifying, repairing, attenuating or inactivatinga target gene or other chromosomal DNA. In one aspect, this disclosure relatesto methods and compositions for gene targeting with high efficiency in a cell.This disclosure also relates to methods of treating or preventing a geneticdisease in an individual in need thereof. Further disclosed are chimericnucleases and vectors encoding chimeric nucleases.