Core Viewpoint - The article discusses the potential of CRISPR activation (CRISPRa) technology in treating SCN2A-related neurodevelopmental disorders, particularly focusing on haploinsufficiency as a common cause of these disorders [3][6][8]. Group 1: Research Findings - SCN2A haploinsufficiency is a leading cause of neurodevelopmental disorders, often resulting in autism, intellectual disability, and in some cases, refractory epilepsy [3]. - A study published in Nature demonstrated that CRISPRa could successfully restore SCN2A levels in a mouse model equivalent to a 10-year-old human, reversing neurodevelopmental disorders [3][6]. - The research team confirmed that restoring Scn2a expression in adolescent mice could rescue related electrophysiological defects [6][8]. Group 2: Methodology - The study utilized adeno-associated virus (AAV) to deliver CRISPRa, correcting intrinsic defects in cortical pyramidal cells, which are primarily responsible for the neurodevelopmental disorders and epilepsy associated with SCN2A haploinsufficiency [6][7]. - Systemic delivery of CRISPRa enabled Scn2a+/− mice to resist chemically induced seizures, indicating the therapeutic potential of this approach [7]. Group 3: Implications and Future Directions - The results suggest that CRISPRa-based therapeutic strategies could effectively rescue SCN2A haploinsufficiency, even when intervention occurs during adolescence [8]. - Regel Therapeutics has obtained licensing from the University of California, San Francisco, to develop therapies targeting SCN2A haploinsufficiency, highlighting the commercial potential of this research [8].