ABSTRACT
Gene targeting already can be used to repair genetic defects in cell culture, but the process is inefficient and much remains to be done if it is to be used in a therapeutic context. This chapter reviews some of the capabilities of gene targeting and their relevance for gene therapy, and considers the current limitations in applying gene targeting to gene therapy and how they might be overcome. The challenge of gene targeting is therefore not unlike that of finding a needle in a haystack: not only are the needles very rare, but the haystack is very large. Mouse embryonic stem cells are by far the most frequently used cells for gene targeting. In contradiction to its name, gene targeting is not limited to the modification of genes: in principle, any region of the genome can be modified, although it is possible that certain regions are refractory to targeting.
