Advances in genome-editing techniques have enabled researchers to create specific genetic modifications in laboratory animals such as mice, rats, fruit flies and zebrafish. This is often done to create models of human diseases that can be studied to learn about their etiology, pathology and mechanisms and to test potential therapeutic strategies. But many human diseases can be appropriately modeled only in primates, and, until recently, genome editing in primates has been largely unsuccessful as well as prohibitively expensive, with the only reported successes in generating transgenic primates achieved by using the technique of virus-mediated gene transfer. The viral vector strategy lacks the efficiency and precision required for broad utility, however. Now, researchers led by Weizhi Ji of the Yunnan Key Laboratory of Primate Biomedical Research (Kunming, China) have successfully applied two advanced genome-editing techniques in monkeys, producing cynomolgus macaques with targeted genomic modifications.

The first technique, dubbed the CRISPR/Cas9 system, uses short RNA sequences to direct gene editing, enabling alterations at the single-base-pair level. Ji's team disrupted two target genes simultaneously in macaque embryos by co-injecting the embryos with Cas9 mRNA and guiding RNA. The embryos were transferred to surrogate female macaques, resulting in 10 pregnancies, one of which was later miscarried. At the time the report was published, one female had delivered twin female offspring at full term by caesarean section and the remaining eight females were mid-gestation. Preliminary analyses of tissues from the infant monkeys showed that the CRISPR/Cas9 system resulted in site-specific gene modification with no off-target effects (Cell 156, 836–843; 2014). Further analyses will be forthcoming when the remaining infants are delivered and when the transgenic monkeys reach adulthood.

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Ji's team also investigated the use of the TALEN system in editing macaque genomes. This technique uses special nucleases to bind and cut DNA at a specified genomic location, creating specific mutations. In this case, the targeted gene encodes methyl-CpG binding protein 2 (MECP2), mutations of which are associated with Rett syndrome, an X-linked disorder that affects human females. Six surrogate females became pregnant after transfer of modified embryos, and one female infant was born and had reached 4 months of age at the time the report was published (Cell Stem Cell, 14, 1–6; 2014). Successful MECP2 mutagenesis with no off-target effects was reported.

Together, the studies' results show that in vivo genome editing is possible in nonhuman primates, which may enable the development of better models of human diseases.