The classical method for gene modification is homologous recombination. The benefit of recombination is its use of recombinases, which allow DNA segments to become inverted or deleted (e.g. to â€˜knock-outâ€™ a gene). They can also start translation at designated sites. This ability to accurately pinpoint genes is what initially allowed researchers an extra degree of freedom to the otherwise riskier approach of gene-knockout.
Today, recombinases provide researchers with an ability to precisely control the gene activity in vivo. This approach has been the widely preferred method to generate a germ line â€˜knock-outâ€™ or â€˜knock-inâ€™ within mouse embryonic stem cells . One disadvantage to using the classical approach is that it typically takes more than a year to generate a genetically modified mouse. These kind of applications, however, have added greatly to our understanding of gene activity in vivo. The use of recombination continues to deliver fundamental insights into the most complex biological phenomena such as development, behavior, and disease.