On August 8, 2013, Prof. Qi Zhou’s team from State Key Laboratory of Reproductive Biology, Institute of Zoology, CAS, published their research paper “Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems” on Nature Biotechnology. They achieved simultaneously knockout multiple genes in rat using CRISPR-Cas technology for the first time. 

Rat is a widely used model animal in biomedical study and drug test. Rats are physiologically closer to human than mice. They are also easier to handle because of their larger body size. However, gene knockout rats are not as widely used as mice due to the lag of genome-modification methods in rat. The CRISPR-Cas system achieves targeted genome mutation by the guidance of small RNAs, which make the genome-modification system programmable and multiplexable. Prof. Qi Zhou’s team applied CRISPR-Cas technology in rat and successfully obtained Tet1/Tet2/Tet3 gene triple-mutated rats. They showed in the paper that single gene biallelic knockout could be achieved with a 100% efficiency and triple-gene knockout with a high efficiency up to 60%. Moreover, they demonstrated the mutations induced by the CRISPR-Cas system could transit to the next generation through germline transmission. 

The progress is believed to push forward the development of knockout rat models and their use in biomedical research and drug discovery.