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Researchers from Jilin University Used A New Base Editor to Successfully Implement Single-base Precise Mutations in Rabbits

Release Time:2018-07-16  Publisher:  Preview times:



Professor Lai Liangxue’s group used the new base editor (BE3 and ABE7.10) for the first time to successfully cultivate model rabbits including albinism, double gluteal, progeria, and X-linked dilated cardiomyopathy, and accurately simulated the occurrence and development of similar diseases. Related research results, with Jilin University as the first author unit, were published online in Nature communications (Highly efficient RNA-guided base editing in rabbit, DOI:10.1038/s41467-018-05232-2) on July 13th.

The establishment of animal models that accurately simulate human genetic diseases is essential for studying the mechanism of disease and developing new treatments. The CRISPR/Cas9 system, a highly efficient gene editing technology that has emerged in recent years, has been widely used to construct animal models of human genetic diseases. This system is like a pair of scissors, which can cut genes in the DNA chain, causing random insertion or mutation of nucleotides, or even deletion of large fragments. However, most human genetic diseases are caused by single nucleotide mutations. Therefore, it is difficult to accurately simulate single-base mutations in human diseases using traditional CRISPR/Cas9 systems. In order to further improve the efficiency of single-base precise mutation, recently, a single-base editing system (BE3) and a new adenine base editor (ABE7.10) combining CRISPR/Cas9 and cytosine deaminase have been reported. It can specifically realize C·G to T·A or A·T to G·C base conversion without causing DNA double-strand breaks, avoiding random insertions or deletions caused by repairing broken ends of nucleic acid strands, and large The amplitude reduces the CRISPR/Cas9 off-target rate. At present, the new single-base editing system (BE3, ABE7.10), as an important gene editing tool, has been applied to related research fields such as human disease treatment, animal model preparation, and animal and plant breeding.

As a commonly used experimental animal in the field of biomedicine, rabbits are closer to humans in terms of genetics, physiology, anatomy and nervous system, and can more realistically simulate the pathogenesis of human diseases. Therefore, in order to construct animal models of diseases that are more similar to human diseases, the research team used BE3 and ABE7.10 new base editing systems to accurately target and simulate nonsense mutations, missense mutations and RNA miscuts in human diseases. And successfully constructed disease model rabbits such as albinism (Tyr nonsense mutation), double muscle buttocks (Mstn nonsense mutation, HGPS premature aging (LmnaRNA wrong splicing) and X-linked dilated cardiomyopathy (Dmd missense mutation).

The efficient application of this system in gene-edited rabbits not only provides an ideal disease animal model for the pathogenesis of related diseases and preclinical studies. At the same time, it lays a theoretical basis for accurately targeting single-gene mutations in animal husbandry, improving the productivity of livestock, and breeding new disease-resistant varieties.

Liu Zhiquan, an undergraduate from College of Animal Science, Chen Mao, a graduate student  and Chen Siyu, an undergraduate student from College of Veterinaryl Medicine, are the co-first authors of the paper. Li Zhanjun from College of Animal Science and Lai Liangxue from College of Animal Medicine are the co-corresponding authors. The research was funded by the special project of the National Key Research and Development Program'Stem Cell and Transformation Research'.

Link to the thesis: https://www.nature.com/articles/s41467-018-05232-2



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