Researchers Achieve First Precise Primate Gene ModificationResearchers Achieve First Precise Primate Gene Modification

Genetically modified monkeys have been successfully grown by Chinese scientists. In a paper published in the January 30 issue of the journal Cell, the authors describe how they achieved precise gene modification in monkeys for the first time. This milestone could lead to new avenues for the development of more effective treatments for a range of human diseases.

The team attempted to modify the genomes of single-cell-stage cynomolgus monkey (macaque) embryos in three specific genes. MIT Technology Review says, "The infant macaques show that targeted genome editing is feasible in primates--a potential boon for scientists studying complex diseases, including neurological ones, and an advance that suggests that the method could one day work in humans."

Study coauthor Wezhi Ji says that the three genes were one that regulates metabolism, another that regulates immune cell development, and a third that regulates stem cells and sex determination.

The scientists used a gene editing tool called Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) with an enzyme known as Cas9. This combination, the CRISPR/Cas9 system, is a gene editing tool that can target specific DNA sequences in the genome. Cas9 proteins are directed by molecules called single-guide RNAs to specific sites in the genome. There they generate mutations by introducing double-stranded DNA breaks. Writing for MIT Technology Review, Susan Young gives an in-depth description of the technique here.

Sequencing the genomic DNA from 15 modified embryos, the team found that two of the three targeted genes had mutated in eight of them. Those embryos were then implanted in surrogate females, one of which gave birth to a pair of twins. After the twins were born, the scientists sequenced their DNA and found that the modifications had "taken" in two of the three targeted sites.

Led by Jiahao Sha, PhD, director of the Laboratory of Reproductive Medicine, Nanjing Medical University, the team also included Xingxu Huang, PhD, Nanjing University; and Weizhi Ji, Yunnan Key Laboratory of Primate Biomedical Research (Kunming). There were also 25 other authors of the study listed.

Sha says, "Our study shows that the CRISPR/Cas9 system enables simultaneous disruption of two target genes in one step without producing off-target mutations, Considering that many human diseases are caused by genetic abnormalities, targeted genetic modification in monkeys is invaluable for the generation of human disease models."

Robert Desimone, director of MIT's McGovern Brain Institute for Brain Research, told MIT Technology Review that he and colleagues are planning on using genome editing to create modified monkeys. "Although mice are giving us tremendous insight into basic brain biology and the biology of the disease, there's still a big gap in between the mouse brain and the monkey brain," says Desimone.

Stephen Levy is a contributor to Qmed and MPMN.