Genome Editing

Above: The genomes of these twin infant macaques were modified with multiple mutations.

The ability to create primates with intentional mutations could provide powerful new ways to study complex and genetically baffling brain disorders.

The use of a genome-tool to create two monkeys with specific genetic mutations.

The ability to modify targeted genes in primates is a valuable tool in the study of human diseases.

By Christina Larson

Until recently, Kunming, capital of Chinas southwestern Yunnan province, was known mostly for its palm trees, its blue skies, its laid-back vibe, and a steady stream of foreign backpackers bound for nearby mountains and scenic gorges. But Kunmings reputation as a provincial backwater is rapidly changing. On a plot of land on the outskirts of the citywilderness 10 years ago, and today home to a genomic research facilityscientists have performed a provocative experiment. They have created a pair of macaque monkeys with precise genetic mutations.

Last November, the female monkey twins, Mingming and Lingling, were born here on the sprawling research campus of Kunming Biomedical International and its affiliated Yunnan Key Laboratory of Primate Biomedical Research. The macaques had been conceived via in vitro fertilization. Then scientists used a new method of DNA engineering known as CRISPR to modify the fertilized eggs by editing three different genes, and they were implanted into a surrogate macaque mother. The twins healthy birth marked the first time that CRISPR has been used to make targeted genetic modifications in primatespotentially heralding a new era of biomedicine in which complex diseases can be modeled and studied in monkeys.

CRISPR, which was developed by researchers at the University of California, Berkeley, Harvard, MIT, and elsewhere over the last several years, is already transforming how scientists think about genetic engineering, because it allows them to make changes to the genome precisely and relatively easily (see Genome Surgery, March/April). The goal of the experiment at Kunming is to confirm that the technology can create primates with multiple mutations, explains Weizhi Ji, one of the architects of the experiment.

Ji began his career at the government-affiliated Kunming Institute of Zoology in 1982, focusing on primate reproduction. China was a very poor country back then, he recalls. We did not have enough funding for research. We just did very simple work, such as studying how to improve primate nutrition. Chinas science ambitions have since changed dramatically. The campus in Kunming boasts extensive housing for monkeys: 75 covered homes, sheltering more than 4,000 primatesmany of them energetically swinging on hanging ladders and scampering up and down wire mesh walls. Sixty trained animal keepers in blue scrubs tend to them full time.

The lab where the experiment was performed includes microinjection systems, which are microscopes pointed at a petri dish and two precision needles, controlled by levers and dials. These are used both for injecting sperm into eggs and for the gene editing, which uses guide RNAs that direct a DNA-cutting enzyme to genes. When I visited, a young lab technician was intently focused on twisting dials to line up sperm with an egg. Injecting each sperm takes only a few seconds. About nine hours later, when an embryo is still in the one-cell stage, a technician will use the same machine to inject it with the CRISPR molecular components; again, the procedure takes just a few seconds.

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Genome Editing