Homologous recombination in human embryonic stem cells: a tool for advancing cell therapy and understanding and treating human disease.

Human embryonic stem cells (hESCs) hold great promise for ushering in an era of novel cell therapies to treat a wide range of rare and common diseases, yet they also provide an unprecedented opportunity for basic research to yield clinical benefit. HESCs can be used to better understand human development, to model human diseases, to understand the contribution of specific mutations to the pathogenesis of disease, and to develop human cell-based screening systems to identify novel therapeutic agents and evaluate potential toxicity of therapeutic agents under development. Such basic research will benefit greatly from efficient methods to perform targeted gene modification, an area of hESC investigation that is currently in its infancy. Moreover, the reality of hESC-based cellular therapies will require improved methods for generating the specific cells of interest, and reporter cell lines generated through targeted gene modifications are expected to play an important role in developing optimal cell-specific differentiation protocols. Herein, we review the current status of homologous recombination in hESCs, a gene targeting technique that is sure to continue to improve, and to play an important role in realizing the maximal human benefit from hESCs.