先导编辑与碱基编辑双线出击 基因编辑治疗脑疾病曙光初现

Core Viewpoint - Recent advancements in gene editing technology, particularly through pioneering editing techniques, show promise in treating severe neurological diseases, although significant technical and funding challenges remain to be addressed [1][4]. Group 1: Breakthroughs in Gene Editing - Harvard University and Jackson Laboratory successfully utilized pioneering editing technology to correct pathogenic gene mutations in a mouse model of Alternating Hemiplegia of Childhood (AHC), achieving an 85% mutation correction rate [2]. - The treatment led to significant improvements in the mice's brain function, reducing seizure frequency and doubling their lifespan, alongside enhancements in motor and cognitive abilities [2]. - A separate team, led by Professor Qiu Zilong, demonstrated the ability to reverse behavioral abnormalities in MEF2C mutation mice using base editing technology, which is crucial for addressing epilepsy and developmental disorders in children [2][3]. Group 2: Safety and Feasibility - The precision of gene editing technology allows for targeted correction of pathogenic mutations, making it an ideal treatment for neurodevelopmental disorders and autism in children [3]. - The pioneering editing technique requires only a single brain injection for treatment, with minimal off-target effects, confirming its safety and feasibility [3]. - The technology has shown the capability to simultaneously correct five mutations, indicating its broad applicability [3]. Group 3: Challenges Ahead - Despite promising results in mouse models, significant hurdles remain before gene editing can benefit human patients, including the need for advanced delivery systems to target brain cells effectively [4]. - The use of adeno-associated virus 9 (AAV9) as a delivery vehicle poses risks of severe immune reactions at high doses, necessitating the development of improved viral vectors and exploration of non-viral delivery methods [4]. - The biotechnology sector is currently facing a funding crisis, which complicates the lengthy and complex development processes for gene therapies, potentially deterring investors [5].