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Gene-edited disease scab cloned in China

  Gene-edited disease carcasses cloned in China
Five cloned monkeys from somatic cells of a redesigned monkey with disease phenotypes Credit: © Science China Press

The first cohort of five redesigned monkey clones made from fibroblasts of a monkey with disease phenotypes was recently born at the Chinese Academy of Sciences (CAS) in Shanghai, the Institute of Neuroscience (ION). The term BMAL1

, a nuclear circadian regulatory transcription factor, was knocked out in the donor lab using CRISPR / Cas9 mediated embryonic gene digestion, and donor abdominal fibroblasts were used to clone five monkeys using the somatic cell nuclear transfer method, same method that generated Zhong Zhong and Hua Hua, the first two cloned monkeys, last year. This major advance, reported in two articles in the journal National Science Review on January 24, demonstrates that a population of customized, genetically-engineered, reshaped macaques will soon be available for biomedical research.

The first article describes the generation of redesigned donor cells using CRISPR-Cas9 to edit the BMAL1 gene of in vitro fertilized monkey embryos. These monkeys exhibited a wide variety of circulatory phenotypes, including reduced sleep time, elevated night-time motifs, diminished circadian blood hormone cycling, increased anxiety and depression, and schizophrenia-like behavior. "Disorders of the circadian rhythm can lead to many human diseases, including sleep disorders, diabetes mellitus, cancer and neurodegenerative diseases. Thus, our BMAL1 outcome monkeys could be used to study disease pathogenesis as well as therapeutic treatments," said Hung-Chun Chang, senior author and investigator of Chinese Academy of Science Institute of Neuroscience. The second article describes the cloning of macaques from the fibroblasts of a BMAL1 knockout monkey using the method of somatic cell nuclear transfer. In this method, the researchers removed the nucleus from an ape-oocyte (egg cell) and replaced it with another nucleus from a fibroblast, a differentiated somatic (body) cell. This reconstructed egg then evolved into an embryo carrying the genes of the replacement nucleus.

The embryo was then transferred to the uterus by a surrogate female monkey who later gave birth to the cloned monkey. In the previous work, Zhong Zhong and Hua Hua were generated using fibroblasts from a killed fetus. The current work succeeded in using fibroblasts from a young adult re-edited donor monkey with disease phenotypes. "Our approach is to perform gene editing in fertilized embryos to first generate a group of redesigned monkeys, and then select a monkey that shows correct gene editing and most severe disease phenotypes as the donor abbot for cloning by somatic cell nuclear transfer," said Qiang Sun, senior author of the paper nuclear transfer. and Director of ION's Nonhuman Primate Research Facility. "We believe that this approach to cloning redesigned monkeys could be used to generate a variety of monkey models for gene-based diseases, including many brain diseases, as well as immune and metabolic disorders and cancer." The researchers plan to continue to improve the technique to increase the efficiency of cloning. The group expects several macaque clones that carry pathogenic gene mutations to be generated in the coming years.

A video of five cloned monkeys. Credit: Science China Press

Department of Neuroscience, CAS follows strict international guidelines for animal research. "This work required coordinated efforts from many laboratories and serves as a clear example of the effective teamwork strongly emphasized by CAS," said Muhammad Poo, a co-author of both studies, who heads the Institute of Neuroscience and helps monitor the project. . "This research line will help reduce the amount of macaque monkeys currently used in biomedical research around the world." "Without the interference of genetic background, a much smaller number of cloned monkeys bearing disease phenotypes may be sufficient for preclinical tests of therapeutic efficacy effects," says Poo.

First monkeys cloned by a process that made Dolly the sheep

More Information :
Qiu, P. et al.: "BMAL1 knockout macaque monkeys show reduced sleep and psychiatric disorders". National Science Review . DOI: 10.1093 / nsr / nwz002, https://academic.oup.com/nsr/article-lookup/doi/10.1093/nsr/nwz002

Liu, Z. et al. "Cloning of a redesigned macaque monkey by somatic cell nuclear transfer". National Science Review . DOI: 10.1093 / nsr / nwz003, https://academic.oup.com/nsr/article-lookup/doi/10.1093/nsr/nwz003

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Gene-edited disease scab cloned in China (2019, January 23)
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