Y. NIU ET AL/CELL 2014

Two female cynomolgus monkeys named Mingming and Ningning are the first primates to have their genes precisely edited by scientists.

The two cynomolgus monkeys, also known as crab-eating macaques, are the first primates to have their genes precisely edited using a gene-snipping tool borrowed from bacteria, a team of Chinese scientistsreports January 30 inCell. The work is part of an effort to genetically engineer monkeys to produce mutations like those seen in human diseases, especially ones involving the brain.

Other researchers have inserted foreign genes into primates (SN: 6/20/09, p. 13), but until now, no one has succeeded in altering the animals own genes, says Guoping Feng, a neurobiologist at the McGovern Institute for Brain Research at MIT who was not involved in the work.

To alter the monkeys genes, Jiahao Sha of Nanjing Medical University and his colleagues wielded molecular scissors first discovered in bacteria. The scissors are a DNA-cutting enzyme called Cas9. In bacteria, Cas9 is part of a primitive immune system known as CRISPRs that defends against viruses by chopping up ones that the bacteria have encountered before and recognize as threats.

The technique has been used to edit the genes of human cells growing in laboratory dishes and in rats, mice and other laboratory organisms, but never before in a living primate.

Sha, along with Xingxu Huang of Nanjing University and Weizhi Ji of the Yunnan Key Laboratory of Primate Biomedical Research and Kunming Biomed International, injected mRNA used to produce Cas9 into single-celled monkey embryos. At the same time, the researchers inserted other small RNA molecules that would guide the enzyme to three genes the scientists wanted to disrupt. Once the enzyme reached the genes, it would snip the DNA, leaving the cell to attempt a repair. In some cases, the cell would be unable to repair the break correctly, leading to disruption of the genes activity.

Researchers hope to use the technique to disrupt genes linked to human diseases so they can study how the disease develops and test treatments. For this study, the researchers chose three genes to disrupt:NrOb1, which is involved in keeping embryonic stem cells flexible and for determining sex;Ppar-gamma, which helps regulate metabolism; andRag1, an immune system gene.

The researchers found that two of the three targeted genes had been simultaneously altered in eight of 15 injected embryos. Those eight embryos were transplanted into surrogate mothers. The researchers delivered the first two female babies, named Mingming and Ningning, from one of the surrogate moms on November 11, 2013. Both infants carry disruptedPpar-gammaandRag1genes. Two of the other surrogates miscarried, and the researchers said in an e-mail that they are awaiting the birth of the remaining baby monkeys.

Only the targeted genes were disrupted, the researchers reported. That fact is encouraging, says Jennifer Doudna, a biochemist and Howard Hughes Medical Institute investigator at the University of California, Berkeley who is a pioneer of CRISPR techniques. It suggests that CRISPRs could be used to repair some human genes without inadvertently damaging others.

Read more here:
Scientists Genetically Engineered Monkeys To Have Human Diseases

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