Zinc finger nuclease technology heralds a new era in mammalian transgenesis

Non-mouse mammalian transgenesis is limited by its overall inefficiency and technical hurdles. Recent years have seen the emergence of two approaches that are applicable to most mammals. The first, based on lentivirus vectors, allows efficient generation of transgenic founders, most of them expressing the transgene. The second, recently applied to produce transgenic fish and mammals, takes advantage of the design of specific ‘DNA-scissors’ for efficient introduction of subtle mutations in potentially any region of the genome. This review focuses on the potential of this latter technology to modify mammalian genomes without the need to apply challenging and less-efficient protocols. We highlight the complementary aims of these new approaches and the as-yet-unexplored possibilities offered by their combination.