Laboratory of
Disease Models in Non-Human Primates
Research Interests

Genetically modified (GM) animals represent a crucial tool for understanding gene function in development and disease. The type II bacterial CRISPR/Cas system has been demonstrated as an efficient gene-targeting technology to generate mice carrying mutations and reporter. However, GM animals generated by CRISPR/Cas9 system are mosaicism, in which two or more populations of cells with different genomes are present in an individual animal. It is costly and time consuming to produce single-gene knockout animal and even more so to make double-mutant animal through the germline transmission of chimeric animals, especially for non-human primate, due to its longer sexual maturity lengths (4 to 5years) as compared to rodents.

Thus, we applied three strategies to generate different types of GM animals.

First, knockout monkey: we optimized CRISPR/Cas9 system and obtained fully functional knockout mice and monkey in F0, which could be directly used for phenotypical analysis. These results indicate that this approach will make genetic studies in monkeys much more realistic in the future.

Second, knockin monkey: we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage on both transgene donor vector (containing guide RNA target sites and ~ 800 bp homology arms) and targeted genome. We found HMEJ-based method achieved transgene integration in mouse and monkey embryos, as well as hepatocytes and neurons in vivo, with an efficiency much higher than other knockin strategies. Thus, HMEJ-based strategy may be useful for a variety of applications, such as gene editing for generating animal models and targeted gene therapies.

Third, transgene monkey with gene overexpression: Using lentivirus infection, we could obtain transgene monkey with single or multiple genes overexpression.

Through these three methods, we could generate many types of GM monkeys. In the near future, we will focus on generating several monkey disease models, including PD, and monkey tool models, including optogenetic monkeys, neuron-specific Cre monkeys.

In addition, we also study on CRISPR/Cas9 technology, including CRISPR activation, CRISPR labeling and gene therapy. Furthermore, we are interested in interspecie generation and its application.

Overall, we sincerely invite scientists to join us and welcome research enthusiasts to do a visiting study in our lab.

For postdoctoral application: Strong motivation, skilled in writing, no limitation for major.



Yang, Hui, Ph.D.

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