methods for modifying a target genomic locus in a cell, for enhancing homologous recombination at a target genomic locus in a cell, and for producing an f0 generation from a nonhuman animal.

摘要

The present invention relates to methods and compositions for producing one or more target genetic modifications at a target genomic locus in a cell and for producing non-human animals comprising the target genomic locus. The methods employ two or more large targeting vectors that are able to recombine with each other and with the target genomic locus in a single step of genomic targeting. The methods may also be employed in combination with a nuclease agent. Methods and compositions for enhancing homologous recombination at a target genomic locus in a cell are also provided. The methods employ two or more nucleic acids comprising one or more overlapping sequences. The methods may be employed in combination with a nuclease agent or without a nuclease agent.