Animal modeling: transgenic monkeys may be a new hope for overcoming human diseases

  Anthony Chan spent two years using human genes for the first time and raised five monkeys through genetic mutations to study Huntington's disease. However, according to a report in 2008, three monkeys showed severe symptoms of Huntington's disease. The onset rate was much faster than expected and must be terminated within the first month of life. This exacerbates the condition of the subject, and is a disadvantage of using animal disease models for research, because the virus used to produce the relevant gene randomly executes other copies in the subject. Relief.

  Chan is a geneticist at Emory University in Atlanta, Georgia. Currently, he and scientists all over the world are watching the development of advanced gene editing technologies that use enzymes and RNA to replace viruses. Solved a series of problems. Many people have high hopes for this problem, hoping that recombinant monkeys will more realistically imitate human genetic conditions than mice and will better create conditions for drug development and testing. Yes. Many people say that primate experiments have accelerated basic research in the field of neuroscience, enabling researchers to map the brain to detect complex neural circuits. Chen said: "This is something we never thought of."

  Next month, the Salk Institute for Biology in La Jolla, California will host a seminar where molecular biologists, bioengineers and neuroscientists will discuss how to solve a series of problems in the field. Terrence Sejnowski, head of the Computational Neurobiology Laboratory at the Salk Institute, said: "These studies have great potential."

  Neuroscientists have been keen to breed genetically modified monkeys. Because primates lack complex cognitive and social abilities, they cannot fully reproduce diseases such as autism, schizophrenia, and Alzheimer's disease in mice. However, researchers have always insisted on experimenting with mice because there are some target gene editing methods that work mainly in animals. It relies on very rare voluntary DNA exchange activities to change or turn off certain genes. The maintenance and selection cost of mouse stem cells is very low, the sexual maturity cycle is short, and many offspring can be reproduced. Edward Callaway, a neuroscientist at the Salk Institute, said: "It is much cheaper to use mice as experimental subjects than monkeys."

  But thanks to effective gene editing technology, researchers can modify the embryos one by one. Therefore, monkeys can be used as experimental subjects. One method is to use zinc finger nucleases to track specific gene regions and cut the gene so that researchers can interfere with its function or replace it with external DNA. Another method called CRISPR is to use special DNA fragments to induce DNA lytic enzymes to make them work in designated areas. Feng Zhang, a synthetic biologist at the Massachusetts Institute of Technology (MIT), demonstrated how CRISPR works in May. Multiple genes in mouse embryos can be accurately mutated. Zhang believes that this method paves the way for using the monkey model to study human brain damage, because human brain damage is also affected by multiple genes. Robert Desimon of the McGovern Institute for Brain Science at MIT said: "It is now possible to perform experiments on primates. This is unprecedented. You can try some experiments that can be used for gene-related treatments. Diseases. Method." MIT researchers are collaborating with researchers at the National Primate Research Center in Oregon to test the effects of CRISPR on fertilized monkey eggs. They have begun to study the research that causes the gene to lose its original function. Feng Guoping (one of Zhang’s colleagues), a neuroscientist at the Massachusetts Institute of Technology, intends to interfere with a gene called SHANK3 that is associated with some human cases of autism. Zhang said that if you want to make more complex changes to a gene, such as swapping it for another gene, you need more research and design.

  Zhang said that CRISPR could eventually be used to mark specific nerve types in monkeys, or to control these neurons through light. Scientists call mouse neurons. He added that the same method can now be used to control it. Neuroscientists especially hope that these new methods will succeed. In the past decade, scientists have begun to use genetic tools to stimulate, inhibit or record neural activity in mice and fruit flies. Anthony Movshon, a monkey vision researcher at New York University, is paying attention to this. But he believes that mice and fruit flies do not have high research value in certain important areas of neuroscience (such as cognition, attention, memory and decision-making abilities).

  These new developments are exciting, but with its development, monkey research has become more and more difficult. Under pressure from animal rights activists, United Airlines announced in January that it would suspend the transportation of monkeys for research purposes. This means that the last airline in North America that allows the transportation of primates has closed the door for researchers. The New England Primate Research Center in Massachusetts also announced in April that it will gradually move animals from the center to other research institutions and then close it completely. Despite the controversy, some researchers believe that using recombinant monkeys may be the best way to treat brain diseases and explore how neurons produce consciousness. I will. Movhong said: "Researchers hope that the experimental model can match the problem being studied. It is unethical to use mice that are not suitable for them."