The "Non-Human Primate Research Platform" of CEBSIT is a dedicated research facility established in June 2009. Initially, from 2009 to 2019, the platform utilized the experimental space and animal facilities provided by Suzhou Xishan Zhongke Laboratory Animal Company. Over the past decade, the platform has evolved into a leading international facility specializing in non-human primate laboratory animal breeding, conservation, model animal development, and talent training.
Sun Qiang is the Director of the Platform. His career in laboratory animal management, model animal development, and related research began during his master's studies at Yangzhou University (1996-1999). After earning his PhD in 2005, he led a subproject of the 973 Program focused on the "Research on Reproductive Physiology of Monkeys and the Construction of Transgenic Monkeys," delving into research on non-human primate laboratory animals. Notably, in 2007, he achieved a significant milestone by obtaining the first batch of "test-tube crab-eating monkeys" in China.
In June 2009, Sun Qiang joined the Institute of Neuroscience at the Chinese Academy of Sciences as a senior engineer, where he was instrumental in establishing the non-human primate research platform. By 2018, he was promoted to senior researcher and doctoral supervisor. His distinguished contributions have been recognized with several accolades, including the National Outstanding Youth Fund, designation as a leading young and middle-aged scientific and technological innovator by the Ministry of Science and Technology, the "10,000 Talents Plan" by the Organization Department of the Central Committee, the 2018 Tan Jiazhen Life Science Innovation Award, the 2019 Special Government Allowance of the State Council, and the 2020 Wuxi Apptec Life Chemistry Research Award Scholar.
Currently, he serves as the Executive Director of the Primate Laboratory Animal Committee of the Chinese Society of Experimental Animals, the Director of the Shanghai Society of Experimental Animals, and a member of the Biosafety Professional Committee of the Shanghai Society of Experimental Animals.
Scientific Research and Technological Innovation
Experimental animals are indispensable in life sciences and medical research. Compared to rodents such as rats and mice, non-human primate experimental animals are more evolutionarily similar to humans. Their anatomical and functional similarities to humans provide a natural advantage in studying various disease mechanisms and developing effective therapies. They have played an irreplaceable role in vaccine development, blood transfusion, and the establishment of deep brain stimulation techniques.
While genetic manipulation techniques in mice have been established and refined to enable precise genetic modifications such as point mutations, tissue-specific expression, single allele knockout, large fragment insertion, and regulated expression, making mice the most widely used model animals in life sciences, the experimental results based on mouse models often fail to replicate the pathological features of human diseases, particularly brain diseases. This limitation has hindered the development of drugs for severe brain diseases such as Alzheimer's and Parkinson's, which pose significant threats to human health and quality of life.
With the advent of transgenic and gene editing technologies, it has become possible to construct non-human primate models that accurately simulate human diseases. This has led to rapid advancements in transgenic, gene editing, and somatic cell nuclear transfer technologies in non-human primates, marking them as cutting-edge technologies in recent years. Our research group primarily focuses on non-human primate experimental animals, with supplementary work on rodent models, to conduct research on assisted reproduction, model animal construction, population genetics, stem cells, early embryonic development, somatic cell reprogramming, gut microbiota-host interactions, experimental animal cultivation, animal welfare, and the ethics of animal experimentation.
1. Development and Technological Research of Non-Human Primate Model Animals
We have utilized lentiviral transfection and gene editing techniques based on molecular nuclease and base editing to construct various primate models, including those for autism (Nature 2016), circadian rhythm disorders (National Science Review 2019a), and epileptic encephalopathy (Molecular Therapy 2022). We have also established and optimized efficient gene editing technologies using CRISPR/Cas (Cell Research 2017 & 2018, Nucleic Acids Research 2020).
We will continue to use these technologies to develop non-human primate models for human diseases that cannot be addressed by rodent models. Additionally, we will focus on breeding and conservation of existing models, and explore new research avenues including but not limited to acute induction and organoid-based non-human primate models. Our goal is to rapidly, efficiently, and accurately construct non-human primate models and advance the application of existing models.
2. Study on the Reprogramming Mechanisms of Cloned Primate Embryos
In 2018, we successfully created cloned monkeys using somatic cell nuclear transfer (Cell 2018), and the following year, we generated cloned offspring of BMAL1 gene-edited monkeys using the same technique (National Science Review 2019b). Although we have established somatic cell nuclear transfer technology in non-human primates, the birth rate of cloned monkeys remains low, and the epigenetic mechanisms affecting the development of cloned primate embryos are not yet fully understood.
To address these issues, we will continue to investigate the epigenetic regulation mechanisms involved in primate somatic cell reprogramming. Our goal is to identify the factors that hinder the development of cloned primate embryos and to enhance the efficiency of somatic cell nuclear transfer in monkeys.
3. Research on Primate Reproductive Physiology and Ovarian Aging
The rhesus monkey and crab-eating macaque are ideal experimental animals for studying reproductive physiology and ovarian aging due to their menstrual cycles and single births. As female primates age, the number of primordial follicles in their ovaries decreases, leading to a decline in reproductive capacity. This decline continues until the primordial follicles are exhausted and menopause occurs.
Serum levels of Anti-Müllerian Hormone (AMH) are used to assess ovarian reserve, predict ovarian response during assisted reproductive processes, evaluate ovarian reserve in cancer patients, aid in the diagnosis of polycystic ovary syndrome and premature ovarian failure, and forecast menopause. We have analyzed age-related changes in AMH levels in female crab-eating macaques and rhesus monkeys (General and Comparative Endocrinology 2018), and attempted to predict the response to exogenous gonadotropin stimulation based on serum AMH levels in crab-eating macaques (Endocrine Connections 2018).
Given the advantages of non-human primate models in studying female reproductive endocrinology and physiology, we will utilize aged monkeys from our platform to explore the patterns of ovarian aging and perimenopausal reproductive physiological changes.
4. Research on Assisted Reproductive Technologies for Non-Human Primates
Mice are characterized by their short time to sexual maturity, high reproductive efficiency, and numerous inbred strains with consistent genetic backgrounds. In contrast, commonly used non-human primate models, such as rhesus macaques and crab-eating macaques, have a longer time to sexual maturity—taking 4-5 years—and typically reproduce only one offspring at a time, resulting in limited reproductive efficiency.
Improving reproductive efficiency and reducing the time to sexual maturity in non-human primates can significantly enhance their utility in biological and medical research and provide valuable insights into reproductive preservation under specific conditions, such as in cancer patients.
In our previous work, we achieved early passage in crab-eating macaques using testicular xenografting (Cell Research 2016) and exogenous hormone stimulation (National Science Review 2021). Additionally, to address the medical needs and safety concerns related to mitochondrial genetic diseases, we developed the first polar body transfer technology in monkeys and produced offspring in crab-eating macaques (Cell Research 2021).
We will continue to develop new assisted reproductive technologies for non-human primates, integrating these advancements with gene editing and population genetics to enhance model construction and specialized breeding efforts.
5. Animal Welfare and Ethics in Experimental Research
Ensuring the welfare of laboratory animals is crucial for the accuracy and reproducibility of scientific results. We are committed to treating laboratory animals with humane principles and conducting experiments under ethical guidelines. To enhance the management of animal facilities and improve animal welfare, as well as to promote the principles of animal research ethics, we will explore scientific approaches and methods that promote animal health and reduce stress and pain. This includes research on microbiota-host interactions, paired housing, and stress reduction techniques to improve overall animal welfare.
