Precise modifications of complex genomes at the single nucleotide level have been one of the big goals for scientists working in basic and applied genetics,including biotechnology,drug development,gene therapy and synthetic biology.However,the relevant techniques for making these manipulations in model organisms and human cells have been lagging behind the rapid high throughput studies in the post-genomic era with a bottleneck of low efficiency,time consuming and laborious manipulation,and off-targeting problems.Recent discoveries of TALEs(transcription activator-like effectors) coding system and CRISPR(clusters of regularly interspaced short palindromic repeats) immune system in bacteria have enabled the development of customized TALENs(transcription activator-like effector nucleases) and CRISPR/Cas9 to rapidly edit genomic DNA in a variety of cell types,including human cells,and different model organisms at a very high efficiency and specificity.In this review,we first briefly summarize the development and applications of TALENs and CRISPR/Cas9-mediated genome editing technologies;compare the advantages and constraints of each method;particularly,discuss the expected applications of both techniques in the field of site-specific genome modification and stem cell based gene therapy;finally, propose the future directions and perspectives for readers to make the choices.