AAV9-mediated transduction of memory circuits following convection-enhanced delivery into the olfactory bulbs.

IF 4.5 3区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Theodore Dimitrov, Vikas Munjal, Allison O'Brien, Matthew T Rocco, Ahmad Karkhah, Kaya E Ceyhan, Daniel Prevedello, Lluis Samaranch
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引用次数: 0

Abstract

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.

aav9介导的记忆电路在对流增强传递到嗅球后的转导。
本研究探索了腺相关病毒血清型9 (AAV9)将治疗基因直接传递到贯穿嗅球(OB)的记忆回路中的潜力,嗅球是一个关键的记忆和感觉处理区域。利用编码绿色荧光蛋白(GFP)的AAV9的对流增强传递(CED),我们绘制了从OB到关键记忆相关脑区(包括内嗅皮质(EC)和海马)的广泛神经连接。我们的研究结果揭示了神经通路的重要转导,并强调了针对OB连接组进行进行性神经退行性疾病(如阿尔茨海默病或轻度认知障碍)治疗干预的潜力。针对OB连接组将为新的治疗策略铺平道路,以保持神经元功能和减缓进展,提供一个有希望的途径,超越症状缓解,以解决疾病的潜在机制。
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来源期刊
Gene Therapy
Gene Therapy 医学-生化与分子生物学
CiteScore
9.70
自引率
2.00%
发文量
67
审稿时长
4-8 weeks
期刊介绍: Gene Therapy covers both the research and clinical applications of novel therapeutic techniques based on a genetic component. Over the last few decades, significant advances in technologies ranging from identifying novel genetic targets that cause disease through to clinical studies, which show therapeutic benefit, have elevated this multidisciplinary field to the forefront of modern medicine.
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