Precise gene editing in monkeys paves the way for valuable human disease models
Precise gene editing in monkeys paves
the way for valuable human disease models
Posted by:
Tarun Kumar
A Monkeys are important for modeling
diseases because of their close similarities to humans, but pa
st efforts to
precisely modify genes in primates have failed. In a study published by Cell
Press January 30th in the journal Cell, researchers achieved precise gene
modification in monkeys for the first time using an efficient and reliable
approach known as the CRISPR/Cas9 system. The study opens promising new avenues
for the development of more effective treatments for a range of human diseases.
"Our
study shows that the CRISPR/Cas9 system enables simultaneous disruption of two
target genes in one step without producing off-target mutations," says
study author Jiahao Sha of Nanjing Medical University. "Considering that
many human diseases are caused by genetic abnormalities, targeted genetic
modification in monkeys is invaluable for the generation of human disease
models."
The
CRISPR/Cas9 system is a gene editing tool capable of targeting specific DNA
sequences in the genome. Cas9 proteins, which are directed by molecules called
single-guide RNAs to specific sites in the genome, generate mutations by
introducing double-stranded DNA breaks. Until now, the CRISPR/Cas9 system and
other targeted gene editing techniques were successfully applied to mammals
such as mice and rats, but not to primates.
Sha teamed
up with Xingxu Huang of Nanjing University and Weizhi Ji of the Yunnan Key
Laboratory of Primate Biomedical Research and Kunming Biomed International. The
researchers injected messenger RNA molecules encoding Cas9, in addition to
single-guide RNAs designed to target three specific genes, into one-cell-stage
embryos of cynomolgus monkeys. After sequencing genomic DNA from 15 embryos,
they found that eight of these embryos showed evidence of simultaneous
mutations in two of the target genes.
The
researchers then transferred genetically modified embryos into surrogate
females, one of which gave birth to a set of twins. By sequencing the twins'
genomic DNA, they found mutations in two of the target genes. Moreover, the
CRISPR/Cas9 system did not produce mutations at genomic sites that were not
targeted, suggesting that the tool will not cause undesirable effects when
applied to monkeys. "With the precise genomic targeting of the CRISPR/Cas9
system, we expect that many disease models will be generated in monkeys, which
will significantly advance the development of therapeutic strategies in
biomedical research," Ji says.
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Source:
The above
story is based on materials provided by Cell Press. Note: Materials may be
edited for content and length.
Journal
Reference:
Yuyu Niu,
Bin Shen, Yiqiang Cui, Yongchang Chen, Jianying Wang, Lei Wang, Yu Kang,
Xiaoyang Zhao, Wei Si, Wei Li et al. Generation of Gene-Modified Cynomolgus
Monkey via Cas9/RNA-Mediated Gene Targeting in One-Cell Embryos. Cell, 30
January 2014 DOI: 10.1016/j.cell.2014.01.027