Gene modifications in animal models have been greatly facilitated through the 
application of targeted genome editing tools. The prokaryotic CRISPR/Cas9 type 
II genome editing system has recently been applied in cell lines and 
vertebrates. However, we still have very limited information about the 
efficiency of mutagenesis, germline transmission rates and off-target effects in 
genomes of model organisms. We now demonstrate that CRISPR/Cas9 mutagenesis in 
zebrafish is highly efficient, reaching up to 86.0%, and is heritable. The 
efficiency of the CRISPR/Cas9 system further facilitated the targeted knock-in 
of a protein tag provided by a donor oligonucleotide with knock-in efficiencies 
of 3.5-15.6%. Mutation rates at potential off-target sites are only 1.1-2.5%, 
demonstrating the specificity of the CRISPR/Cas9 system. The ease and efficiency 
of the CRISPR/Cas9 system with limited off-target effects make it a powerful 
genome engineering tool for in vivo studies.