HKUST develops new gene editing strategies to help treat Alzheimer's disease

An international research team led by the Hong Kong University of Science and Technology (HKUST) has recently successfully developed a new type of whole-brain gene editing technology, which has been shown to improve the pathological symptoms of Alzheimer’s disease (AD) in a mouse model and has the potential to develop into AD New long-acting treatment.

It is estimated that more than 500,000 people in China suffer from inherited Alzheimer's disease, that is, familial Alzheimer's disease (FAD). FAD is a congenital Alzheimer's disease that is highly related to family history. Although patients with FAD have a clear genetic cause and can be diagnosed before cognitive problems, there is currently no effective treatment.

Gene editing technology * has shown great potential in the treatment of diseases caused by genetic mutations such as FAD. It can correct the genetic mutation that causes the disease before the symptoms of the disease appear, and can achieve the therapeutic effect of "one-time treatment, long-term effective". However, there are still some obstacles to the clinical development and application of gene editing technology. For example, there is currently a lack of effective, efficient, and non-invasive delivery tools to deliver gene editing tools to the brain. In addition, the existing genome editing technology is still unable to play an effective therapeutic role in the whole brain.

Recently, a research team led by Professor Ye Yuru, Vice President (Research and Development) of the University of Science and Technology, has developed a new type of whole-brain gene editing technology. This technology uses a new type of delivery tool that can cross the blood-brain barrier and deliver optimized gene editing tools to the entire brain through a single, non-invasive intravenous injection to achieve efficient whole-brain gene editing. Studies have found that this technology can effectively destroy the FAD gene mutation in the AD transgenic mouse model, and improve the pathological symptoms of AD in the whole brain, laying the foundation for the development of new AD treatment methods.

At the same time, the research team also found that after 6 months of treatment with gene editing technology, AD transgenic mice, which is one-third of the average life span of mice, have amyloid plaques in their brains that are thought to cause AD neurodegeneration. , Still maintains a low level, proving that the single treatment of this gene editing technology can maintain long-term curative effects. The study also did not find any obvious side effects in mice.

The research team demonstrates that disruption of a familial Alzheimer's disease mutation by this genome editing strategy reduces disease pathology, ie the area of ​​Aβ deposition, throughout the brain.

Professor Ye, who is also the Professor of Life Sciences at HKUST and Director of the State Key Laboratory of Molecular Neuroscience, said: "Our research has achieved efficient whole-brain gene editing for the first time, and at the same time effectively improved the pathological symptoms of AD in the whole brain. It is an exciting development, and it is an important milestone in the application of gene editing technology to the treatment of hereditary brain diseases, which will help promote the development of precision medicine for related diseases."

This research was carried out in collaboration with a research team from the University of Science and Technology, California Institute of Technology, and Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences. Research results have been awarded by international authoritative scientific journals"Nature Biomedical Engineering"Published.

* Gene editing is a biotechnology that precisely modifies the genome of an organism by deleting, inserting, or replacing DNA sequences at specific locations in the genome.