Dimitrov Theodore, Munjal Vikas, O'Brien Allison, Rocco Matthew T, Karkhah Ahmad, Ceyhan Kaya E, Prevedello Daniel, Samaranch Lluis
Department of Neurological Surgery, The Ohio State University, Columbus, OH, USA.
Gene Therapy Institute, The Ohio State University, Columbus, OH, USA.
Gene Ther. 2025 Jul 26. doi: 10.1038/s41434-025-00555-4.
This study explores the potential of adeno-associated virus serotype 9 (AAV9) to deliver therapeutic genes directly into the memory circuit throughout the olfactory bulb (OB), a critical memory and sensory processing region. Using convection-enhanced delivery (CED) of AAV9 encoding green fluorescent protein (GFP), we mapped the extensive neural connectivity from the OB to key memory-related brain regions, including the entorhinal cortex (EC) and hippocampus. Our findings reveal significant transduction of neural pathways and underscore the potential of targeting the OB connectome for therapeutic interventions in progressive neurodegenerative disorders such as Alzheimer's disease or mild cognitive impairment. Targeting the OB connectome will pave the way for new therapeutic strategies to preserve neuronal function and slow the progression, offering a promising avenue beyond symptomatic relief to address the underlying mechanisms of the disease.
本研究探讨了9型腺相关病毒（AAV9）将治疗性基因直接递送至整个嗅球（OB）记忆回路的潜力，嗅球是一个关键的记忆和感觉处理区域。通过对流增强递送（CED）编码绿色荧光蛋白（GFP）的AAV9，我们绘制了从嗅球到关键记忆相关脑区（包括内嗅皮层（EC）和海马体）的广泛神经连接图谱。我们的研究结果揭示了神经通路的显著转导，并强调了针对嗅球连接组进行治疗干预以治疗诸如阿尔茨海默病或轻度认知障碍等进行性神经退行性疾病的潜力。针对嗅球连接组将为保护神经元功能和减缓疾病进展的新治疗策略铺平道路，为解决疾病的潜在机制提供了一条超越症状缓解的有前景的途径。
