The CRISPR-Cas9 system from bacteria has been recently employed to generate mutant alleles in a range of different organisms. However, so far it is not clear whether this system can be used for correcting mutations that cause diseases. Recently, a team of researchers from Chinese Academy of Sciences (CAS) successfully cured a disease in a whole animal. 

To test the feasibility of CRISPR-Cas9-mediated genetic repair, Dr. WU Yuxuan, PhD student LIANG Dan and their colleagues, led by Dr. LI Jinsong at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences chose a mouse model of dominant cataract disorder caused by a defined mutation in the Crygc gene. They designed a guide RNA that led Cas9 to the mutant allele where it induced a cleavage of the DNA. After injection of Cas9 mRNA and sgRNA into zygotes carrying heterogenous mutant Crygc gene, about 33 percent of the mutant zygotes grew up to be cataract-free mice. Correction occurred via homology-directed repair (HDR) based on an exogenously supplied oligonucleotide or the endogenous wild type allele. The repaired mice were fertile and able to transmit the corrected allele to their progeny. These results provide proof of principle for use of the CRISPR-Cas9 system to correct genetic disease. 

This work entitled “Correction of a Genetic Disease in Mouse via Use of CRISPR-Cas9” was published in Cell Stem Cell on Dec 5^th, 2013. This study was supported by the grants from the Chinese Academy of Sciences (the Strategic Priority Research Program), the Ministry of Science and Technology, National Natural Science Foundation of China and Shanghai Municipal Commission for Science and Technology.  

CONTACT: 
LI Jinsong 
E-mail: jsli@sibcb.ac.cn 
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 
Shanghai, China

Genetic correction via HDR uses information from endogenous WT allele (top) or from an exogenous oligo (bottom). (Image by Dr. LI Jinsong)