Over the past 5 years there has been a major transformation in our ability to 
precisely manipulate the genomes of animals. Efficiencies of introducing precise 
genetic alterations in large animal genomes have improved 100000-fold due to a 
succession of site-specific nucleases that introduce double-strand DNA breaks 
with a specificity of 10(-9). Herein we describe our applications of 
site-specific nucleases, especially transcription activator-like effector 
nucleases, to engineer specific alterations in the genomes of pigs and cows. We 
can introduce variable changes mediated by non-homologous end joining of DNA 
breaks to inactive genes. Alternatively, using homology-directed repair, we have 
introduced specific changes that support either precise alterations in a gene's 
encoded polypeptide, elimination of the gene or replacement by another unrelated 
DNA sequence. Depending on the gene and the mutation, we can achieve 10%-50% 
effective rates of precise mutations. Applications of the new precision genetics 
are extensive. Livestock now can be engineered with selected phenotypes that 
will augment their value and adaption to variable ecosystems. In addition, 
animals can be engineered to specifically mimic human diseases and disorders, 
which will accelerate the production of reliable drugs and devices. Moreover, 
animals can be engineered to become better providers of biomaterials used in the 
medical treatment of diseases and disorders.