Editor's note: When neurons become silent in diseases and injuries, and traditional treatment methods repeatedly hit walls in complex nervous systems, humans have never stopped yearning for cure. At present, the field of neuroscience has achieved multiple breakthrough research results, including not only laboratory miracles, but also the dawn of clinical progress. These achievements are working together to dispel the fog of medicine. To this end, Science and Technology Daily has launched a series of reports on new breakthroughs in neuroscience research for readers. Even five years ago, people would have thought that DNA repair in living brains was a plot unique to science fiction. But now, scientists have been able to enter the brain, repair mutations, and maintain this repair effect throughout the entire life cycle of cells. On July 21st, the journal Cell published a groundbreaking achievement by an international research team that directly edited DNA in the brain for the first time through a single injection technique. They successfully corrected the genetic mutation that caused the extremely rare disease 'alternating hemiplegia in children' (AHC). The study not only significantly improved the symptoms of experimental mice, but also prolonged their survival period. This technology has also been tested in cells derived from human patients and has shown good repair efficacy and safety. This achievement marks a crucial step forward for gene editing in the treatment of neurological diseases and is considered a major milestone in personalized gene therapy. Brain genes can also accurately correct AHC, which is an extremely rare genetic neurological disease that usually occurs in infancy. It is characterized by sudden paralysis, muscle tone disorders, abnormal eye movement, and epileptic seizures, seriously affecting the quality of life of children and even endangering their lives. There is currently no cure, and treatment mainly focuses on relieving symptoms. The new research is one of the important achievements of the Somatic Genome Editing Alliance of the National Institutes of Health in the United States, jointly led by institutions such as the Jackson Laboratories (JAX) and the Broad Institute. The research team focused on the two most common mutation sites in AHC - D801N and E815K in the ATP1A3 gene, and conducted experiments using a novel mouse model. These mice exhibit severe symptoms and premature death similar to humans, providing an ideal model for testing treatment efficacy. The team tested two next-generation gene editing technologies: gene therapy and Prime editing. Among them, Prime editors performed particularly well. It precisely modified DNA sequences, repaired up to 85% of mutated brain cells, restored normal protein function, significantly improved mouse motility, reduced epileptic seizures, and extended lifespan. We have not yet directly tested it on human patients, but achieving such high repair efficiency in a mouse model is already very exciting. ”Markus Terry, a neuroscientist and co leader of research at JAX, emphasized that this technology platform has high scalability and echoes the recent first case of gene editing therapy for liver genetic diseases, marking the comprehensive entry of gene editing technology into the field of multi system disease treatment. Cleverly opening the door to personalized gene therapy is that this treatment can be completed with just a single injection. It requires the use of a harmless virus called AAV9 as a delivery vector to deliver the Prime editing tool into the brain. The injection should be performed shortly after birth to ensure that the editing tool can act on a large number of neurons as early as possible. In the experiment, the harmless AAV9 virus broke through the blood-brain barrier (a natural protective barrier that had long hindered brain gene therapy). Sending gene editing tools into the brain has always been a major challenge faced by the scientific community. The existence of the blood-brain barrier makes it difficult for most viruses to enter the brain, and the editing efficiency achieved in the brain this time is remarkable, "said Katherine Lutz, co-author of the study and deputy director of the Rare Disease Translational Center at JAX." Studies in cells derived from human patients have shown that the off target effect of this technology is minimal, providing key evidence for the safety of clinical applications. Marcus Terry said, "If we can achieve this for one gene mutation, then it should also be feasible for other mutations. Considering that 80% of rare diseases are hereditary, the application prospects of this achievement are very broad." In other words, as long as the pathogenic site is identified, future doctors can develop targeted gene therapy plans. Igniting hope for "incurable" diseases, AHC patients often suffer from periodic paralysis, epilepsy, and developmental disorders from a young age, and existing therapies can only provide limited relief to symptoms. This study not only brings hope to AHC, but also demonstrates to all hereditary neurological diseases that through precise genetic modification, those diseases that were once deemed "untreatable" may be fundamentally improved through personalized treatment in the future. Liu Ruqian, a member of the American Academy of Sciences and professor at the Broad Institute, is the inventor of Prime editing technology and one of the senior co authors of this study. He called this research an important milestone in Prime editing technology, which could open new doors for treating many neurological disorders that have long been considered 'incurable'. Katherine Lutz pointed out that it is the combination of virus delivery systems and Prime editing technology that has enabled precise brain gene editing to move from science fiction to reality. They are advancing critical testing to explore the feasibility of implementing interventions after symptoms have appeared. If it is proven that this treatment can reverse existing diseases, then it will completely overturn the traditional treatment paradigm. This means that the medical community has taken a revolutionary step in conquering the most complex diseases. (New Society)