Particularly precise genetic modification
Due to their similarity to humans, monkeys are an extremely important experimental model, but until now, genes in the DNA of primates were introduced at the stage of a multicellular embryo and "aimlessly", which led to very low efficiency of such work. Chinese researchers from Nanjing Medical University, working under the leadership of Jiahao Sha, managed to overcome this barrier with an effective and reliable approach known as the CRISPR/Cas9 system.
The CRISPR/Cas9 system, which was included in the top ten achievements of biomedicine in 2013 (according to MIT Technology Review) and science in general (according to Nature), is a tool for gene modification that allows you to change certain DNA sequences in a targeted manner. The principle of operation of this system is that bacterial Cas9 enzymes delivered by means of special guiding RNA molecules to certain regions of the genome generate mutations by creating double-stranded breaks in DNA.
Previously, this approach has been successfully used to modify the genes of small mammals, such as rats and mice. For the first time, the authors managed to achieve a positive result in experiments on monkeys. To do this, they injected informational RNAs encoding the Cas9 enzyme into the fertilized eggs of Javanese macaques, and guiding RNAs that ensure the delivery of Cas9 to target genes. Subsequent DNA sequencing of 15 embryos revealed mutations of two target genes occurring simultaneously in 8 of them.
The diagram and the snapshot below are from an article in Cell
The genetically modified embryos were implanted into surrogate mothers, one of whom gave birth to two twin monkeys. Subsequent sequencing of their genomes also demonstrated the presence of mutations of two target genes.
It is extremely important that the use of the CRISPR/Cas9 system did not lead to the appearance of unintended mutations in other regions of the genome. This eliminates the occurrence of undesirable side effects when using this approach for therapeutic purposes. The authors believe that their results have opened a new direction of research, within the framework of which many monkey models of various diseases will be created, which will make it possible to achieve significant success in the development of new therapeutic strategies.
Article by Yuyu Niu et al. Generation of Gene-Modified Cynomolgus Monkey via Cas9/RNA-Mediated Gene Targeting in One-Cell Embryos is published in the journal Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ScienceDaily:
Precise gene editing in monkeys paves the way for valuable human disease models.
03.02.2014