Genetically Modified Monkeys Using Crispr Genome to Show Transhuman Genome Editing in Humans Are Feasible


(Brian Wang) China has created genetically modified monkeys using a new method of DNA engineering known as Crispr. 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.

The new study shows for the first time that Crispr can create viable primates with genomes modified at specific targeted genes.

The Chinese researchers injected single-cell macaque embryos with RNAs to guide the genome-editing process. The team modified three genes in the monkeys: one that regulates metabolism, another that regulates immune cell development and a third that regulates stem cells and sex determination.

Crispr, on the other hand, can be used to insert, delete, or rewrite a DNA sequence at a specific location within a genome. Like the random viral insertion used by the Emory team, the Crispr method employed by Ji and colIeagues can create genetically modified animals in a single generation, an important consideration for researchers working with animals that can take three years to reach sexual maturity and are expensive and difficult to rear.

Others say they are anxious to use Crispr to create their own monkeys. Robert Desimone, director of MIT’s McGovern Brain Institute for Brain Research, says he and colleagues are planning on using genome editing to create modified monkeys. He says it’s possible the success of the Chinese researchers will encourage other groups to use primates in their work. “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.

The fact that genome editing worked to create modified monkeys suggests it might also work to create genetically modified humans. Crispr is already used to modify human cells grown in labs, but it has not yet been tested on human embryos or adults. “We believe the success of this strategy in nonhuman primates gives lots of potential for its application in humans, but we think due to the safety issue, it will take a long way for expanding this strategy to human embryos,” says Ji.

Several U.S. pioneers of the Crispr system recently founded a startup that will attempt to develop cures for genetic disease using genome-editing technology

Highlights
* CRISPR/Cas9-mediated simultaneous targeting of multiple genes in monkey embryos
* Demonstrates an efficient and reliable approach for genome modified monkey generation
* Achieves Ppar-g and Rag1 double mutation in monkeys in one step

Summary

Monkeys serve as important model species for studying human diseases and developing therapeutic strategies, yet the application of monkeys in biomedical researches has been significantly hindered by the difficulties in producing animals genetically modified at the desired target sites. Here, we first applied the CRISPR/Cas9 system, a versatile tool for editing the genes of different organisms, to target monkey genomes. By coinjection of Cas9 mRNA and sgRNAs into one-cell-stage embryos, we successfully achieve precise gene targeting in cynomolgus monkeys. We also show that this system enables simultaneous disruption of two target genes (Ppar-γ and Rag1) in one step, and no off-target mutagenesis was detected by comprehensive analysis. Thus, coinjection of one-cell-stage embryos with Cas9 mRNA and sgRNAs is an efficient and reliable approach for gene-modified cynomolgus monkey generation.

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