Department of Translational Neuroscience, Division of Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Master's Program Neuroscience and Cognition, Utrecht University, Utrecht, The Netherlands.
Sci Rep. 2019 Jul 31;9(1):11146. doi: 10.1038/s41598-019-47417-9.
Targeting specific neuronal cell types is a major challenge for unraveling their function and utilizing specific cells for gene therapy strategies. Viral vector tools are widely used to target specific cells or circuits for these purposes. Here, we use viral vectors with short promoters of neuropeptide genes to target distinct neuronal populations in the hypothalamus of rats and mice. We show that lowering the amount of genomic copies is effective in increasing specificity of a melanin-concentrating hormone promoter. However, since too low titers reduce transduction efficacy, there is an optimal titer for achieving high specificity and sufficient efficacy. Other previously identified neuropeptide promoters as those for oxytocin and orexin require further sequence optimization to increase target specificity. We conclude that promoter-driven viral vectors should be used with caution in order to target cells specifically.
针对特定的神经元细胞类型是揭示其功能并利用特定细胞进行基因治疗策略的主要挑战。病毒载体工具被广泛用于针对这些目的的特定细胞或回路。在这里，我们使用具有神经肽基因短启动子的病毒载体来靶向大鼠和小鼠下丘脑的不同神经元群体。我们表明，降低基因组拷贝数可有效提高黑皮质素集中激素启动子的特异性。然而，由于太低的滴度会降低转导效率，因此存在实现高特异性和足够疗效的最佳滴度。其他先前确定的神经肽启动子，如催产素和食欲素启动子，需要进一步的序列优化以增加目标特异性。我们得出结论，为了有针对性地靶向细胞，应谨慎使用启动子驱动的病毒载体。
