Recently, investigators have successfully developed powerful systems using alternative technologies (ZFNs, TALENs and CRISPR/Cas9 system) to genetically engineer mice much faster and more economically compared to traditional homologous recombination method. Herein, we applied the CRISPR/Cas9 system to generate mice carrying mutations in multiple glyco-genes which are frequently species-specific in human and mouse. An example of species-specific glyco-gene is an inactivating mutation in humans of the gene Cmah, an enzyme responsible for Neu5Gc biosynthesis from the Neu5Ac form of sialic acid. We planned to identify several mouse-specific glyco-gene and edit them to generate mice with human-like glycan. We expect these glycan-humanized mice can hold great promise as a novel model for non-clinical study that is to provide safety information to support the clinical development of the new pharmaceuticals, thereby playing a pivotal role in bridging the translational gap to a successful clinical outcome. In addition, glycan-humanized mouse models can be anticipated to contribute invaluable information to our knowledge of glycobiology and medicine.