Children with a single functioning copy of the SCN2A gene face SCN2A haploinsufficiency, a leading cause of neurodevelopmental disorders characterized by severe symptoms including seizures and communication difficulties. Researchers from the University of California, San Francisco (UCSF) are exploring the potential of CRISPR technology to mitigate these challenges by enhancing the expression of the functional SCN2A gene.
In a recent publication in Nature, the team detailed their preclinical findings using mice engineered to mimic human mutations. Instead of editing the defective gene, they employed CRISPR activation (CRISPRa) to boost the expression of the healthy copy, resulting in significant improvements in neurodevelopmental outcomes. Notably, the intervention proved effective in younger mice, suggesting that even post-development, therapeutic responses are possible.
Kevin Bender, PhD, co-senior author of the study, noted that the brain’s anatomy remained intact despite the SCN2A deficiency, with synapses failing to mature. By increasing SCN2A levels, they successfully restored signaling pathways, reducing seizure susceptibility. The collaboration with Nadav Ahituv, PhD, led to the design of CRISPRa that effectively doubled the expression of the healthy gene, demonstrating the potential for targeted therapies. While initial results are promising, further investigations are essential to ensure safety and efficacy in human applications, particularly regarding protein levels in patients.
Regel Therapeutics has licensed this CRISPR technology from UCSF to develop treatments for SCN2A haploinsufficiency, indicating a significant step towards clinical applications in neurodevelopmental disorders.
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